Johnson & Johnson showcases latest advancements in cancer innovation with more than 70 clinical and real-world studies at ASCO and EHA

RARITAN, N.J., May 22, 2025 – Johnson & Johnson (NYSE:JNJ) announced today promising new data from its hematologic malignancies and solid tumor portfolio and pipeline will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and at the European Hematology Association (EHA) 2025 Congress. More than 70 abstracts, including 13 oral presentations across both meetings, will feature results from pivotal studies in multiple myeloma, B-cell and myeloid malignancies, lung, prostate, and colorectal cancers. Three additional abstracts at EHA will share data on warm autoimmune hemolytic anemia (wAIHA), a rare autoantibody-driven disease.

“We relentlessly pursue therapies with the potential to change and save lives, and our newest data at this year’s ASCO and EHA meetings are proof of our progress,” said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson Innovative Medicine. “The key to getting in front of cancer is delivering the right medicines at the right time, harnessing our scientific insights to not just manage progression, but change the course of disease.”

“At the center of everything we do is our commitment to transform outcomes for patients with cancer,” said June Lanoue, U.S. President, Hematology, Johnson & Johnson Innovative Medicine. “We’re excited to present the latest clinical trial and real-world data from our diverse oncology portfolio, showcasing our potentially life-changing therapies.”

Key Data Presentations

ASCO Highlights

Multiple Myeloma

• New five-year long-term remission and survival outcomes data from the Phase 1b/2 CARTITUDE-1 study evaluating CARVYKTI^® (ciltacabtagene autoleucel; cilta-cel) in patients with relapsed or refractory multiple myeloma (Oral Abstract #7507)
• Results of survival subgroup analyses from the Phase 3 CARTITUDE-4 study assessing CARVYKTI^® versus standard of care in patients with relapsed or refractory multiple myeloma (Poster Abstract #7539)
• Subgroup analysis from the Phase 3 CEPHEUS study investigating the efficacy and safety of DARZALEX^® (daratumumab) plus bortezomib, lenalidomide, and dexamethasone (D-VRd) in transplant-ineligible (TIE) patients, including frail patients, with newly diagnosed multiple myeloma (NDMM) (Oral Abstract #7516)
• Analysis from the Phase 3 PERSEUS trial of sustained minimal residual disease negativity in transplant-eligible (TE) patients with NDMM receiving subcutaneous DARZALEX^® plus VRd followed by DARZALEX^® plus lenalidomide (DR) maintenance therapy (Oral Abstract #7501)
• Cytogenetic subgroup analysis from the Phase 3 CEPHEUS trial evaluating DARZALEX^® plus bortezomib, lenalidomide, and dexamethasone (D-VRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) in TIE or transplant-deferred (TD) patients with NDMM (Poster Abstract #7529)
• First clinical results from an in-human study investigating JNJ-79635322 for refractory multiple myeloma, highlighting preliminary efficacy and safety outcomes and identifying a recommended Phase 2 dose (Oral Abstract #7505)
• Updated efficacy and safety data from the Phase 1/2 MonumenTAL-1 study evaluating TALVEY^® (talquetamab-tgvs) in patients with relapsed or refractory multiple myeloma, with analyses at an extended median follow-up (Poster Abstract #7528)

B-Cell Malignancies

• Final analysis from the Phase 2 CAPTIVATE study evaluating fixed-duration IMBRUVICA^® (ibrutinib) in combination with venetoclax in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) (Poster Abstract #7036)
• Efficacy and safety analysis of first-line IMBRUVICA^® in combination with venetoclax from the SYMPATICO study in older patients with mantle cell lymphoma and TP53 mutations (Rapid Oral Abstract #7017)

Prostate Cancer

• Late-breaking data from the Phase 3 AMPLITUDE trial evaluating AKEEGA^® (niraparib and abiraterone acetate dual-action tablet) plus prednisone for patients with metastatic castration-sensitive prostate cancer (mCSPC), and alterations in homologous recombination repair genes (Oral Abstract #LBA5006)
• First results from the Phase 1 study of JNJ-78278343 (pasritamig), a novel T-cell engager designed to target KLK2, a highly prostate-specific protein, to drive tumor-specific immune activity in patients with metastatic castration-resistant prostate cancer (mCRPC) (Rapid Oral Abstract #5017)

Lung Cancer

• Patient-reported outcomes from the Phase 2 COCOON study – presented by Jill Feldman, lung cancer survivor and co-founder of the EGFR Resisters, a patient advocacy group – evaluating an enhanced, readily available preventative regimen to reduce dermatologic reactions in patients receiving first-line RYBREVANT^® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) for EGFR-mutated non-small cell lung cancer (NSCLC) (Poster Abstract #8641)
• Outcomes by baseline resistance data from the Phase 3 MARIPOSA-2 study evaluating RYBREVANT^® plus chemotherapy versus chemotherapy alone in patients with NSCLC with epidermal growth factor receptor exon 19 deletions or L858R substitution mutations whose disease progressed on osimertinib (Poster Abstract #8639)

Colorectal Cancer

• First clinical data from the Phase 1b/2 OrigAMI-1 study evaluating amivantamab treatment in patients with refractory metastatic colorectal cancer showing increase in biomarker expression, indicative that amivantamab is harnessing the immune system (Poster Abstract #3550)

EHA Highlights

Multiple Myeloma

• First clinical results from an in-human study investigating JNJ-79635322, a novel trispecific antibody (TsAb) and next-generation immunotherapy, in patients with relapsed or refractory multiple myeloma, highlighting preliminary efficacy and safety outcomes and identifying a recommended Phase 2 dose (Presented as “One of the six best abstracts” during the Plenary Abstracts Session - Oral Abstract #S100)
• Absolute lymphocyte count as a key biomarker for monitoring safety after treatment with CARVYKTI^® (Poster Abstract #PS1728)
• Health-related quality of life data from the DARZALEX^® Phase 3 CEPHEUS trial in patients with transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma (Poster Abstract #PS1763)
• Updated results from Phase 1/2 MonumenTAL-1 of prophylactic tocilizumab and post-treatment dexamethasone with outpatient dosing and mitigation of cytokine release syndrome with TALVEY^® in patients with relapsed or refractory multiple myeloma (Poster Abstract #PS1760)
• Initial safety and efficacy results from the Phase 1b TRIMM-3 study of TALVEY^® in combination with cetrelimab in patients with relapsed or refractory multiple myeloma (Oral Abstract #S200)
• First results from the REALiTAL study observing TALVEY^® in patients with relapsed or refractory multiple myeloma outside of clinical trials (Poster Abstract #PF742)
• Subgroup analysis of the real world evidence REALiTEC study of TECVAYLI^® (teclistamab-cqyv) in patients with relapsed or refractory multiple myeloma outside of clinical trials (Poster Abstract #PF770)
• Long-term follow-up data from the China cohort of the Phase 1/2 MajesTEC-1 study of TECVAYLI^® in patients with relapsed or refractory multiple myeloma (Abstract #PB2950)

B-Cell Malignancies

• First results from a global Phase 1b study evaluating JNJ-90014496, a CD19/CD20 bispecific CAR-T cell therapy, in patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), including determination of the recommended Phase 2 dose and assessment of safety, efficacy and pharmacokinetics (Oral Abstract #S239)
• Final analysis from the Phase 2 CAPTIVATE study evaluating fixed-duration IMBRUVICA^® in combination with venetoclax in patients with CLL and SLL (Oral Abstract #S156)
• Match-adjusted indirect comparison of IMBRUVICA^® in combination with venetoclax versus acalabrutinib in combination with venetoclax in subjects with previously untreated CLL (Poster Abstract #PF587)

Myeloid Malignancies

• Updated Phase 1b data to determine a recommended Phase 2 dose for menin inhibitor bleximenib (JNJ-75276617) in combination with venetoclax and azacitidine in relapsed/refractory or newly diagnosed KMT2Ar or NPM1m acute myeloid leukemia (Oral Abstract #S137)

Warm Autoimmune Hemolytic Anemia

• Advancing research in benign hematologic conditions, three poster presentations on warm autoimmune hemolytic anemia (wAIHA) highlight critical findings on the disease prevalence, treatment patterns, and impact on all-cause mortality. These analyses underscore a significant unmet need for new treatment options with proven safety and efficacy profiles for individuals with wAIHA (Poster Abstracts #PF1206, #PF1208 and #PS2195)

Information on Johnson & Johnson sponsored abstracts is available on JNJ.com.

About AKEEGA^®
AKEEGA^® is a combination, in the form of a dual-action tablet (DAT), of niraparib, a highly selective poly (ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, a CYP17 inhibitor.¹ AKEEGA^® together with prednisone or prednisolone was approved in April 2023 by the European Medicines Agency, and in August 2023 by the FDA, for the treatment of patients with BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC). Additional marketing authorization applications are under review or approved across a number of countries globally.
 
Additional ongoing studies include the Phase 3 AMPLITUDE study, evaluating the combination of AKEEGA^® and prednisone in a biomarker-selected patient population with metastatic castration-sensitive prostate cancer (mCSPC).

About RYBREVANT^®
RYBREVANT^® (amivantamab-vmjw) is approved in the U.S., Europe and other markets around the world in combination with LAZCLUZE™ (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.

RYBREVANT^®, a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, is approved in the U.S., Europe and other markets around the world as monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.²

RYBREVANT^® is approved in the U.S., Europe and other markets around the world in combination with chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test.

RYBREVANT^® is approved in the U.S., Europe and other markets around the world in combination with chemotherapy (carboplatin-pemetrexed) for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR TKI.

In April 2025, the European Medicines Agency (EMA) approved SC amivantamab and LAZCLUZE™ for the first-line treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, and as a monotherapy for the treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy.

The National Comprehensive Cancer Network^® (NCCN^®) Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for NSCLC^§ prefer next-generation sequencing–based strategies over polymerase chain reaction–based approaches for the detection of EGFR exon 20 insertion variants. The NCCN Guidelines include:

• Amivantamab-vmjw (RYBREVANT^®) plus lazertinib (LAZCLUZE™) as a Category 1 recommendation for first-line therapy in patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations.^3†‡
• Amivantamab-vmjw (RYBREVANT^®) plus chemotherapy as a Category 1 recommendation for patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations who experienced disease progression after treatment with osimertinib.^3†‡
• Amivantamab-vmjw (RYBREVANT^®) plus chemotherapy as a Category 1 recommendation for first-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation-positive advanced NSCLC.^3†‡
• Amivantamab-vmjw (RYBREVANT^®) as a Category 2A recommendation for patients that have progressed on or after platinum-based chemotherapy with or without an immunotherapy and have EGFR exon 20 insertion mutation-positive NSCLC.^3†‡

For more information, visit: https://www.RYBREVANT.com.

About LAZCLUZE™
In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of LAZCLUZE™ (marketed as LECLAZA in South Korea). LAZCLUZE™ is an oral, third-generation, brain-penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR. An analysis of the efficacy and safety of LAZCLUZE™ from the Phase 3 LASER301 study was published in The Journal of Clinical Oncology in 2023.⁴

About CARVYKTI^®
CARVYKTI^® (cilta-cel) received U.S. Food and Drug Administration approval in February 2022 for the treatment of adults with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.⁵ In April 2024, CARVYKTI^® was approved in the U.S. fortreatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor, an immunomodulatory agent, and who are refractory to lenalidomide, following a unanimous (11 to 0) FDA Oncologic Drugs Advisory Committee (ODAC) recommendation in support of this new indication. In April 2024, the European Medicines Agency (EMA) approved a Type II variation for CARVYKTI^® for the treatment of adults with relapsed and refractory multiple myeloma who have received at least one prior therapy, including an immunomodulatory agent and a proteasome inhibitor, have demonstrated disease progression on the last therapy, and are refractory to lenalidomide. In September 2022, Japan’s Ministry of Health, Labour and Welfare (MHLW) approved CARVYKTI^® for the treatment of adults with relapsed or refractory multiple myeloma in patients that have no history of CAR-positive T cell infusion therapy targeting BCMA and who have received three or more lines of therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody, and in whom multiple myeloma has not responded to or has relapsed following the most recent therapy.

CARVYKTI^® is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding chimeric antigen receptor (CAR) that directs the CAR-positive T cells to eliminate cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells. The CARVYKTI^® CAR protein features two BCMA-targeting single domains designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.

In December 2017, Janssen Biotech, Inc., a Johnson & Johnson company, entered into an exclusive worldwide license and collaboration agreement with Legend Biotech USA, Inc. to develop and commercialize CARVYKTI^®.

For more information, visit www.CARVYKTI.com.

About DARZALEX FASPRO^® and DARZALEX^®
DARZALEX FASPRO^® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for ten indications in multiple myeloma, three of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.⁶ It is the only subcutaneous CD38-directed antibody approved to treat patients with MM. DARZALEX FASPRO^® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE^® drug delivery technology.

DARZALEX^® (daratumumab) received U.S. FDA approval in November 2015 and is approved in ten indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant eligible and ineligible.⁷

DARZALEX^® is the first CD38-directed antibody approved to treat multiple myeloma.¹⁸ DARZALEX^®-based regimens have been used in the treatment of more than 618,000 patients worldwide.

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.

Since 2020, the National Comprehensive Cancer Network^® (NCCN^®) has recommended daratumumab-based combination regimens for the treatment of newly diagnosed multiple myeloma and relapsed and refractory multiple myeloma.^† For newly diagnosed multiple myeloma in non-transplant candidates, the NCCN^® guidelines recommend daratumumab in combination with lenalidomide and dexamethasone as a Category 1 preferred regimen; daratumumab in combination with bortezomib, melphalan, and prednisone as another recommended Category 1 regimen; and daratumumab in combination with bortezomib, cyclophosphamide, and prednisone as another recommended Category 2A regimen. For newly diagnosed multiple myeloma in transplant candidates, the NCCN^® guidelines recommend daratumumab in combination with bortezomib, lenalidomide and dexamethasone as another recommended Category 2A regimen; daratumumab in combination with bortezomib, thalidomide and dexamethasone as a Category 2A regimen useful in certain circumstances; daratumumab in combination with carfilzomib, lenalidomide and dexamethasone as a Category 2A regimen useful in certain circumstances; and daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone as a Category 2A regimen useful in certain circumstances. For maintenance in transplant candidates, the NCCN guidelines recommend daratumumab in combination with lenalidomide as useful in certain circumstances. In relapsed/refractory myeloma, four daratumumab regimens are listed as Category 1 preferred regimens for early relapses (1-3 prior therapies): daratumumab in combination with lenalidomide and dexamethasone; daratumumab in combination with bortezomib and dexamethasone; daratumumab in combination with carfilzomib and dexamethasone; and daratumumab in combination with pomalidomide and dexamethasone [after one prior therapy including lenalidomide and a proteasome inhibitor (PI)]. The NCCN^® also recommends daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone as another Category 2A regimen for early relapses (1-3 prior therapies) and as monotherapy as a Category 2A regimen useful in certain circumstances for early relapse patients after at least three prior therapies, including a PI and an immunomodulatory agent, or for patients who are double refractory to a PI and an immunomodulatory agent.

For more information, visit www.DARZALEX.com.

About IMBRUVICA^®
IMBRUVICA^® (ibrutinib) is a once-daily oral medication that is jointly developed and commercialized by Janssen Biotech, Inc., and Pharmacyclics LLC, an AbbVie company. IMBRUVICA^® blocks the BTK protein, which is needed by normal and abnormal B cells, including specific cancer cells, to multiply and spread. By blocking BTK, IMBRUVICA^® may help move abnormal B cells out of their nourishing environments and inhibit their proliferation.^8,9,10

IMBRUVICA^® is approved in more than 100 countries and has been used to treat more than 325,000 patients worldwide over the last decade. There are more than 50 company-sponsored clinical trials, including 18 Phase 3 studies, spanning more than 11 years evaluating the efficacy and safety of IMBRUVICA^®.

IMBRUVICA^® was first approved by the U.S. FDA in November 2013, and by the European Commission (EC) in 2014. To date, IMBRUVICA^® has been approved in more than 100 countries/territories for one or more of the following indications: the treatment of adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with or without 17p deletion (del17p); adults with Waldenström’s macroglobulinemia (WM); adults with mantle cell lymphoma (MCL); adults with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy; and adult and pediatric patients aged one year and older with previously treated chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy.¹¹

About TALVEY^®
TALVEY^® (talquetamab-tgvs) received approval from the U.S. FDA in August 2023 as a first-in-class GPRC5D-targeting bispecific antibody for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.¹² Since FDA approval, 1,500 patients were treated with TALVEY^®. The European Commission (EC) granted conditional marketing authorization (CMA) of TALVEY^® ▼(talquetamab-tgvs) in August 2023 as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.¹³
 
TALVEY^® is a bispecific T-cell engaging antibody that binds to the CD3 receptor expressed on the surface of T-cells and G protein-coupled receptor class C group 5 member D (GPRC5D), a novel multiple myeloma target which is highly expressed on the surface of multiple myeloma cells and non-malignant plasma cells, as well as some healthy tissues such as epithelial cells of the skin and tongue.  
  
About TECVAYLI^®
TECVAYLI^® (teclistamab-cqyv) received approval from the U.S. FDA in October 2022 as an off-the-shelf (or ready-to-use) antibody that is administered as a subcutaneous treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.¹⁴ The European Commission (EC) granted TECVAYLI^® conditional marketing authorization (CMA) in August 2022 as monotherapy for the treatment of adult patients with RRMM who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have demonstrated disease progression since the last therapy. In August 2023, the EC granted the approval of a Type II variation application for TECVAYLI^®, providing the option for a reduced dosing frequency of 1.5 mg/kg every two weeks in patients who have achieved a complete response (CR) or better for a minimum of six months. TECVAYLI^® is a first-in-class, bispecific T-cell engager antibody therapy that uses innovative science to activate the immune system by binding to the CD3 receptor expressed on the surface of T-cells and to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells. In February 2024, the U.S. FDA approved the supplemental Biologics License Application (sBLA) for TECVAYLI^® for a reduced dosing frequency of 1.5 mg/kg every two weeks (Q2W) in patients with relapsed or refractory multiple myeloma who have achieved and maintained a CR or better for a minimum of six months.

For more information, visit www.TECVAYLI.com.

RYBREVANT^® IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions

RYBREVANT^® can cause infusion-related reactions (IRR) including anaphylaxis; signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. The median time to IRR onset is approximately 1 hour.

RYBREVANT^® with LAZCLUZE™

RYBREVANT^® in combination with LAZCLUZE™ can cause infusion-related reactions. In MARIPOSA (n=421), IRRs occurred in 63% of patients treated with RYBREVANT^® in combination with LAZCLUZE™, including Grade 3 in 5% and Grade 4 in 1% of patients. The incidence of infusion modifications due to IRR was 54% of patients, and IRRs leading to dose reduction of RYBREVANT^® occurred in 0.7% of patients. Infusion-related reactions leading to permanent discontinuation of RYBREVANT^® occurred in 4.5% of patients receiving RYBREVANT^® in combination with LAZCLUZE™.

RYBREVANT^® with Carboplatin and Pemetrexed

Based on the pooled safety population (n=281), IRR occurred in 50% of patients treated with RYBREVANT^® in combination with carboplatin and pemetrexed, including Grade 3 (3.2%) adverse reactions. The incidence of infusion modifications due to IRR was 46%, and 2.8% of patients permanently discontinued RYBREVANT^® due to IRR.

RYBREVANT^® as a Single Agent

In CHRYSALIS (n=302), IRR occurred in 66% of patients treated with RYBREVANT^®. Among patients receiving treatment on Week 1 Day 1, 65% experienced an IRR, while the incidence of IRR was 3.4% with the Day 2 infusion, 0.4% with the Week 2 infusion, and cumulatively 1.1% with subsequent infusions. Of the reported IRRs, 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range 0.1 to 18 hours) after start of infusion. The incidence of infusion modifications due to IRR was 62% and 1.3% of patients permanently discontinued RYBREVANT^® due to IRR.

Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT^® as recommended. Administer RYBREVANT^® via a peripheral line on Week 1 and Week 2 to reduce the risk of infusion-related reactions. Monitor patients for signs and symptoms of infusion reactions during RYBREVANT^® infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT^® based on severity. If an anaphylactic reaction occurs, permanently discontinue RYBREVANT^®.

Interstitial Lung Disease/Pneumonitis

RYBREVANT^® can cause severe and fatal interstitial lung disease (ILD)/pneumonitis.

RYBREVANT^® with LAZCLUZE™

In MARIPOSA, ILD/pneumonitis occurred in 3.1% of patients treated with RYBREVANT^® in combination with LAZCLUZE™, including Grade 3 in 1.0% and Grade 4 in 0.2% of patients. There was one fatal case (0.2%) of ILD/pneumonitis and 2.9% of patients permanently discontinued RYBREVANT^® and LAZCLUZE™ due to ILD/pneumonitis.

RYBREVANT^® with Carboplatin and Pemetrexed

Based on the pooled safety population, ILD/pneumonitis occurred in 2.1% treated with RYBREVANT^® in combination with carboplatin and pemetrexed with 1.8% of patients experiencing Grade 3 ILD/pneumonitis. 2.1% discontinued RYBREVANT^® due to ILD/pneumonitis.

RYBREVANT^® as a Single Agent

In CHRYSALIS, ILD/pneumonitis occurred in 3.3% of patients treated with RYBREVANT^®, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) permanently discontinued RYBREVANT^® due to ILD/pneumonitis.

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). For patients receiving RYBREVANT^® in combination with LAZCLUZE™, immediately withhold both drugs in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed. For patients receiving RYBREVANT^® as a single agent or in combination with carboplatin and pemetrexed, immediately withhold RYBREVANT^® in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

Venous Thromboembolic (VTE) Events with Concomitant Use of RYBREVANT^® and LAZCLUZE™

RYBREVANT^® in combination with LAZCLUZE™ can cause serious and fatal venous thromboembolic (VTE) events, including deep vein thrombosis and pulmonary embolism. The majority of these events occurred during the first four months of therapy.

In MARIPOSA, VTEs occurred in 36% of patients receiving RYBREVANT^® in combination with LAZCLUZE™, including Grade 3 in 10% and Grade 4 in 0.5% of patients. On-study VTEs occurred in 1.2% of patients (n=5) while receiving anticoagulation therapy. There were two fatal cases of VTE (0.5%), 9% of patients had VTE leading to dose interruptions of RYBREVANT^®, and 7% of patients had VTE leading to dose interruptions of LAZCLUZE™; 1% of patients had VTE leading to dose reductions of RYBREVANT^®, and 0.5% of patients had VTE leading to dose reductions of LAZCLUZE™; 3.1% of patients had VTE leading to permanent discontinuation of RYBREVANT^®, and 1.9% of patients had VTE leading to permanent discontinuation of LAZCLUZE™. The median time to onset of VTEs was 84 days (range: 6 to 777).

Administer prophylactic anticoagulation for the first four months of treatment. The use of Vitamin K antagonists is not recommended. Monitor for signs and symptoms of VTE events and treat as medically appropriate.

Withhold RYBREVANT^® and LAZCLUZE™ based on severity. Once anticoagulant treatment has been initiated, resume RYBREVANT^® and LAZCLUZE™ at the same dose level at the discretion of the healthcare provider. In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue RYBREVANT^® and continue treatment with LAZCLUZE™ at the same dose level at the discretion of the healthcare provider.

Dermatologic Adverse Reactions

RYBREVANT^® can cause severe rash including toxic epidermal necrolysis (TEN), dermatitis acneiform, pruritus, and dry skin.

RYBREVANT^® with LAZCLUZE™

In MARIPOSA, rash occurred in 86% of patients treated with RYBREVANT^® in combination with LAZCLUZE™, including Grade 3 in 26% of patients. The median time to onset of rash was 14 days (range: 1 to 556 days). Rash leading to dose interruptions occurred in 37% of patients for RYBREVANT^® and 30% for LAZCLUZE™, rash leading to dose reductions occurred in 23% of patients for RYBREVANT^® and 19% for LAZCLUZE™, and rash leading to permanent discontinuation occurred in 5% of patients for RYBREVANT^® and 1.7% for LAZCLUZE™.

RYBREVANT^® with Carboplatin and Pemetrexed

Based on the pooled safety population, rash occurred in 82% of patients treated with RYBREVANT^® in combination with carboplatin and pemetrexed, including Grade 3 (15%) adverse reactions. Rash leading to dose reductions occurred in 14% of patients, and 2.5% permanently discontinued RYBREVANT^® and 3.1% discontinued pemetrexed.

RYBREVANT^® as a Single Agent

In CHRYSALIS, rash occurred in 74% of patients treated with RYBREVANT^® as a single agent, including Grade 3 rash in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% of patients, and RYBREVANT^® was permanently discontinued due to rash in 0.7% of patients.
Toxic epidermal necrolysis occurred in one patient (0.3%) treated with RYBREVANT^® as a single agent.

Instruct patients to limit sun exposure during and for 2 months after treatment with RYBREVANT^® or LAZCLUZE™ in combination with RYBREVANT^®. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen. Alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream is recommended for dry skin.

When initiating RYBREVANT^® treatment with or without LAZCLUZE™, administer alcohol-free emollient cream to reduce the risk of dermatologic adverse reactions. Consider prophylactic measures (e.g. use of oral antibiotics) to reduce the risk of dermatologic reactions. If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. For patients receiving RYBREVANT^® in combination with LAZCLUZE™, withhold, reduce the dose, or permanently discontinue both drugs based on severity. For patients receiving RYBREVANT^® as a single agent or in combination with carboplatin and pemetrexed, withhold, dose reduce or permanently discontinue RYBREVANT^® based on severity.

Ocular Toxicity

RYBREVANT^® can cause ocular toxicity including keratitis, blepharitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, eye pruritus, and uveitis.

RYBREVANT^® with LAZCLUZE™

In MARIPOSA, ocular toxicity occurred in 16% of patients treated with RYBREVANT^® in combination with LAZCLUZE™, including Grade 3 or 4 ocular toxicity in 0.7% of patients. Withhold, reduce the dose, or permanently discontinue RYBREVANT^® and continue LAZCLUZE™ based on severity.

RYBREVANT^® with Carboplatin and Pemetrexed

Based on the pooled safety population, ocular toxicity occurred in 16% of patients treated with RYBREVANT^® in combination with carboplatin and pemetrexed. All events were Grade 1 or 2.

RYBREVANT^® as a Single Agent

In CHRYSALIS, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients treated with RYBREVANT^®. All events were Grade 1-2.

Promptly refer patients with new or worsening eye symptoms to an ophthalmologist. Withhold, reduce the dose, or permanently discontinue RYBREVANT^® based on severity.

Embryo-Fetal Toxicity
Based on its mechanism of action and findings from animal models, RYBREVANT^® and LAZCLUZE™ can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to the fetus.

Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT^®.

Advise females of reproductive potential to use effective contraception during treatment with LAZCLUZE™ and for 3 weeks after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with LAZCLUZE™ and for 3 weeks after the last dose.

Adverse Reactions

RYBREVANT^® with LAZCLUZE™

For the 421 patients in the MARIPOSA clinical trial who received RYBREVANT^® in combination with LAZCLUZE™, the most common adverse reactions (≥20%) were rash (86%), nail toxicity (71%), infusion-related reactions (RYBREVANT^®, 63%), musculoskeletal pain (47%), stomatitis (43%), edema (43%), VTE (36%), paresthesia (35%), fatigue (32%), diarrhea (31%), constipation (29%), COVID-19 (26%), hemorrhage (25%), dry skin (25%), decreased appetite (24%), pruritus (24%), nausea (21%), and ocular toxicity (16%). The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased albumin (8%), decreased sodium (7%), increased ALT (7%), decreased potassium (5%), decreased hemoglobin (3.8%), increased AST (3.8%), increased GGT (2.6%), and increased magnesium (2.6%).

Serious adverse reactions occurred in 49% of patients who received RYBREVANT^® in combination with LAZCLUZE™. Serious adverse reactions occurring in ≥2% of patients included VTE (11%), pneumonia (4%), ILD/pneumonitis and rash (2.9% each), COVID-19 (2.4%), and pleural effusion and infusion-related reaction (RYBREVANT^®) (2.1% each). Fatal adverse reactions occurred in 7% of patients who received RYBREVANT^® in combination with LAZCLUZE™ due to death not otherwise specified (1.2%); sepsis and respiratory failure (1% each); pneumonia, myocardial infarction, and sudden death (0.7% each); cerebral infarction, pulmonary embolism (PE), and COVID-19 infection (0.5% each); and ILD/pneumonitis, acute respiratory distress syndrome (ARDS), and cardiopulmonary arrest (0.2% each).

RYBREVANT^® with Carboplatin and Pemetrexed

For the 130 patients in the MARIPOSA-2 clinical trial who received RYBREVANT^® in combination with carboplatin and pemetrexed, the most common adverse reactions (≥20%) were rash (72%), infusion-related reactions (59%), fatigue (51%), nail toxicity (45%), nausea (45%), constipation (39%), edema (36%), stomatitis (35%), decreased appetite (31%), musculoskeletal pain (30%), vomiting (25%), and COVID-19 (21%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased neutrophils (49%), decreased white blood cells (42%), decreased lymphocytes (28%), decreased platelets (17%), decreased hemoglobin (12%), decreased potassium (11%), decreased sodium (11%), increased alanine aminotransferase (3.9%), decreased albumin (3.8%), and increased gamma-glutamyl transferase (3.1%).

In MARIPOSA-2, serious adverse reactions occurred in 32% of patients who received RYBREVANT^® in combination with carboplatin and pemetrexed. Serious adverse reactions in >2% of patients included dyspnea (3.1%), thrombocytopenia (3.1%), sepsis (2.3%), and pulmonary embolism (2.3%). Fatal adverse reactions occurred in 2.3% of patients who received RYBREVANT^® in combination with carboplatin and pemetrexed; these included respiratory failure, sepsis, and ventricular fibrillation (0.8% each).

For the 151 patients in the PAPILLON clinical trial who received RYBREVANT^® in combination with carboplatin and pemetrexed, the most common adverse reactions (≥20%) were rash (90%), nail toxicity (62%), stomatitis (43%), infusion-related reaction (42%), fatigue (42%), edema (40%), constipation (40%), decreased appetite (36%), nausea (36%), COVID-19 (24%), diarrhea (21%), and vomiting (21%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased albumin (7%), increased alanine aminotransferase (4%), increased gamma-glutamyl transferase (4%), decreased sodium (7%), decreased potassium (11%), decreased magnesium (2%), and decreases in white blood cells (17%), hemoglobin (11%), neutrophils (36%), platelets (10%), and lymphocytes (11%).

In PAPILLON, serious adverse reactions occurred in 37% of patients who received RYBREVANT^® in combination with carboplatin and pemetrexed. Serious adverse reactions in ≥2% of patients included rash, pneumonia, ILD, pulmonary embolism, vomiting, and COVID-19. Fatal adverse reactions occurred in 7 patients (4.6%) due to pneumonia, cerebrovascular accident, cardio-respiratory arrest, COVID-19, sepsis, and death not otherwise specified.

RYBREVANT^® as a Single Agent

For the 129 patients in the CHRYSALIS clinical trial who received RYBREVANT^® as a single agent, the most common adverse reactions (≥20%) were rash (84%), IRR (64%), paronychia (50%), musculoskeletal pain (47%), dyspnea (37%), nausea (36%), fatigue (33%), edema (27%), stomatitis (26%), cough (25%), constipation (23%), and vomiting (22%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased lymphocytes (8%), decreased albumin (8%), decreased phosphate (8%), decreased potassium (6%), increased alkaline phosphatase (4.8%), increased glucose (4%), increased gamma-glutamyl transferase (4%), and decreased sodium (4%).

Serious adverse reactions occurred in 30% of patients who received RYBREVANT^®. Serious adverse reactions in ≥2% of patients included pulmonary embolism, pneumonitis/ILD, dyspnea, musculoskeletal pain, pneumonia, and muscular weakness. Fatal adverse reactions occurred in 2 patients (1.5%) due to pneumonia and 1 patient (0.8%) due to sudden death.

LAZCLUZE™ Drug Interactions

Avoid concomitant use of LAZCLUZE™ with strong and moderate CYP3A4 inducers. Consider an alternate concomitant medication with no potential to induce CYP3A4.

Monitor for adverse reactions associated with a CYP3A4 or BCRP substrate where minimal concentration changes may lead to serious adverse reactions, as recommended in the approved product labeling for the CYP3A4 or BCRP substrate.

Please read full Prescribing Information for RYBREVANT^®.

Please read full Prescribing Information for LAZCLUZE™.

AKEEGA^® IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS
The safety population described in the WARNINGS and PRECAUTIONS reflect exposure to AKEEGA^® in combination with prednisone in BRCAm patients in Cohort 1 (N=113) of MAGNITUDE.

Myelodysplastic Syndrome/Acute Myeloid Leukemia
AKEEGA^® may cause myelodysplastic syndrome/acute myeloid leukemia (MDS/AML).
MDS/AML, including cases with fatal outcome, has been observed in patients treated with niraparib, a component of AKEEGA^®.
All patients treated with niraparib who developed secondary MDS/cancer-therapy-related AML had received previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.
For suspected MDS/AML or prolonged hematological toxicities, refer the patient to a hematologist for further evaluation. Discontinue AKEEGA^® if MDS/AML is confirmed.

Myelosuppression
AKEEGA^® may cause myelosuppression (anemia, thrombocytopenia, or neutropenia).
In MAGNITUDE Cohort 1, Grade 3-4 anemia, thrombocytopenia, and neutropenia were reported, respectively in 28%, 8%, and 7% of patients receiving AKEEGA^®. Overall, 27% of patients required a red blood cell transfusion, including 11% who required multiple transfusions. Discontinuation due to anemia occurred in 3% of patients.
Monitor complete blood counts weekly during the first month of AKEEGA^® treatment, every two weeks for the next two months, monthly for the remainder of the first year and then every other month, and as clinically indicated. Do not start AKEEGA^® until patients have adequately recovered from hematologic toxicity caused by previous therapy. If hematologic toxicities do not resolve within 28 days following interruption, discontinue AKEEGA^® and refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics.

Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions
AKEEGA^® may cause hypokalemia and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. In post-marketing experience, QT prolongation and Torsades de Pointes have been observed in patients who develop hypokalemia while taking abiraterone acetate, a component of AKEEGA^®. Hypertension and hypertensive crisis have also been reported in patients treated with niraparib, a component of AKEEGA^®.
In MAGNITUDE Cohort 1, which used prednisone 10 mg daily in combination with AKEEGA^®, Grades 3-4 hypokalemia was detected in 2.7% of patients on the AKEEGA^® arm and Grades 3-4 hypertension were observed in 14% of patients on the AKEEGA^® arm.

The safety of AKEEGA^® in patients with New York Heart Association (NYHA) Class II to IV heart failure has not been established because these patients were excluded from MAGNITUDE.

Monitor patients for hypertension, hypokalemia, and fluid retention at least weekly for the first two months, then once a month. Closely monitor patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia, or fluid retention, such as those with heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia. Control hypertension and correct hypokalemia before and during treatment with AKEEGA^®.

Discontinue AKEEGA^® in patients who develop hypertensive crisis or other severe cardiovascular adverse reactions.

Hepatotoxicity
AKEEGA^® may cause hepatotoxicity.

Hepatotoxicity in patients receiving abiraterone acetate, a component of AKEEGA^®, has been reported in clinical trials. In post-marketing experience, there have been abiraterone acetate-associated severe hepatic toxicity, including fulminant hepatitis, acute liver failure, and deaths.

In MAGNITUDE Cohort 1, Grade 3-4 ALT or AST increases (at least 5 x ULN) were reported in 1.8% of patients. The safety of AKEEGA^® in patients with moderate or severe hepatic impairment has not been established as these patients were excluded from MAGNITUDE.

Measure serum transaminases (ALT and AST) and bilirubin levels prior to starting treatment with AKEEGA^®, every two weeks for the first three months of treatment and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring and may require dosage modifications.
Permanently discontinue AKEEGA^® for patients who develop a concurrent elevation of ALT greater than 3 x ULN and total bilirubin greater than 2 x ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation, or in patients who develop ALT or AST ≥20 x ULN at any time after receiving AKEEGA^®.

Adrenocortical Insufficiency

AKEEGA^® may cause adrenal insufficiency.

Adrenocortical insufficiency has been reported in clinical trials in patients receiving abiraterone acetate, a component of AKEEGA^®, in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress. Monitor patients for symptoms and signs of adrenocortical insufficiency, particularly if patients are withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress. Symptoms and signs of adrenocortical insufficiency may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with abiraterone acetate. If clinically indicated, perform appropriate tests to confirm the diagnosis of adrenocortical insufficiency. Increased doses of corticosteroids may be indicated before, during, and after stressful situations.

Hypoglycemia

AKEEGA^® may cause hypoglycemia in patients being treated with other medications for diabetes.

Severe hypoglycemia has been reported when abiraterone acetate, a component of AKEEGA^®, was administered to patients receiving medications containing thiazolidinediones (including pioglitazone) or repaglinide.

Monitor blood glucose in patients with diabetes during and after discontinuation of treatment with AKEEGA^®. Assess if antidiabetic drug dosage needs to be adjusted to minimize the risk of hypoglycemia.

Increased Fractures and Mortality in Combination with Radium 223 Dichloride

AKEEGA^® with prednisone is not recommended for use in combination with Ra-223 dichloride outside of clinical trials.

The clinical efficacy and safety of concurrent initiation of abiraterone acetate plus prednisone/prednisolone and radium Ra 223 dichloride was assessed in a randomized, placebo-controlled multicenter study (ERA-223 trial) in 806 patients with asymptomatic or mildly symptomatic castration-resistant prostate cancer with bone metastases. The study was unblinded early based on an Independent Data Monitoring Committee recommendation.

At the primary analysis, increased incidences of fractures (29% vs 11%) and deaths (39% vs 36%) have been observed in patients who received abiraterone acetate plus prednisone/prednisolone in combination with radium Ra 223 dichloride compared to patients who received placebo in combination with abiraterone acetate plus prednisone.

It is recommended that subsequent treatment with Ra-223 not be initiated for at least five days after the last administration of AKEEGA^®, in combination with prednisone.

Posterior Reversible Encephalopathy Syndrome

AKEEGA^® may cause Posterior Reversible Encephalopathy Syndrome (PRES).

PRES has been observed in patients treated with niraparib as a single agent at higher than the recommended dose of niraparib included in AKEEGA^®.
Monitor all patients treated with AKEEGA^® for signs and symptoms of PRES. If PRES is suspected, promptly discontinue AKEEGA^® and administer appropriate treatment. The safety of reinitiating AKEEGA^® in patients previously experiencing PRES is not known.

Embryo-Fetal Toxicity

The safety and efficacy of AKEEGA^® have not been established in females. Based on animal reproductive studies and mechanism of action, AKEEGA^® can cause fetal harm and loss of pregnancy when administered to a pregnant female.

Niraparib has the potential to cause teratogenicity and/or embryo-fetal death since niraparib is genotoxic and targets actively dividing cells in animals and patients (e.g., bone marrow).

In animal reproduction studies, oral administration of abiraterone acetate to pregnant rats during organogenesis caused adverse developmental effects at maternal exposures approximately ≥ 0.03 times the human exposure (AUC) at the recommended dose.

Advise males with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of AKEEGA^®. Females who are or may become pregnant should handle AKEEGA^® with protection, e.g., gloves.

Based on animal studies, AKEEGA^® may impair fertility in males of reproductive potential.

ADVERSE REACTIONS

The safety of AKEEGA^® in patients with BRCAm mCRPC was evaluated in Cohort 1 of MAGNITUDE.

The most common adverse reactions (≥10%), including laboratory abnormalities, are decreased hemoglobin, decreased lymphocytes, decreased white blood cells, musculoskeletal pain, fatigue, decreased platelets, increased alkaline phosphatase, constipation, hypertension, nausea, decreased neutrophils, increased creatinine, increased potassium, decreased potassium, increased AST, increased ALT, edema, dyspnea, decreased appetite, vomiting, dizziness, COVID-19, headache, abdominal pain, hemorrhage, urinary tract infection, cough, insomnia, increased bilirubin, weight decreased, arrhythmia, fall, and pyrexia.

Serious adverse reactions reported in >2% of patients included COVID-19 (7%), anemia (4.4%), pneumonia (3.5%), and hemorrhage (3.5%). Fatal adverse reactions occurred in 9% of patients who received AKEEGA^®, including COVID-19 (5%), cardiopulmonary arrest (1%), dyspnea (1%), pneumonia (1%), and septic shock (1%).

DRUG INTERACTIONS

Effect of Other Drugs on AKEEGA^®

Avoid coadministration with strong CYP3A4 inducers.

Abiraterone is a substrate of CYP3A4. Strong CYP3A4 inducers may decrease abiraterone concentrations, which may reduce the effectiveness of abiraterone.

Effects of AKEEGA^® on Other Drugs

Avoid coadministration unless otherwise recommended in the Prescribing Information for CYP2D6 substrates for which minimal changes in concentration may lead to serious toxicities. If alternative treatments cannot be used, consider a dose reduction of the concomitant CYP2D6 substrate drug.
Abiraterone is a CYP2D6 moderate inhibitor. AKEEGA^® increases the concentration of CYP2D6 substrates, which may increase the risk of adverse reactions related to these substrates.

Monitor patients for signs of toxicity related to a CYP2C8 substrate for which a minimal change in plasma concentration may lead to serious or life-threatening adverse reactions.

Abiraterone is a CYP2C8 inhibitor. AKEEGA^® increases the concentration of CYP2C8 substrates, which may increase the risk of adverse reactions related to these substrates.

Please see the full Prescribing Information for AKEEGA^®.

CARVYKTI^® IMPORTANT SAFETY INFORMATION

INDICATIONS AND USAGE

CARVYKTI^® (ciltacabtagene autoleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide.

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED and RECURRENT CYTOPENIA, and SECONDARY HEMATOLOGICAL MALIGNANCIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with CARVYKTI^®. Do not administer CARVYKTI^® to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which may be fatal or life-threatening, occurred following treatment with CARVYKTI^®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with CARVYKTI^®. Provide supportive care and/or corticosteroids as needed.

Parkinsonism and Guillain-Barré syndrome (GBS) and their associated complications resulting in fatal or life-threatening reactions have occurred following treatment with CARVYKTI^®.

Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, occurred in patients following treatment with CARVYKTI^®. HLH/MAS can occur with CRS or neurologic toxicities.

Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery occurred following treatment with CARVYKTI^®.

Secondary hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia, have occurred in patients following treatment with CARVYKTI^®. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI^®.

CARVYKTI^® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI^® REMS Program.

WARNINGS AND PRECAUTIONS

Increased early mortality - In CARTITUDE-4, a (1:1) randomized controlled trial, there was a numerically higher percentage of early deaths in patients randomized to the CARVYKTI^® treatment arm compared to the control arm. Among patients with deaths occurring within the first 10 months from randomization, a greater proportion (29/208; 14%) occurred in the CARVYKTI^® arm compared to (25/211; 12%) in the control arm. Of the 29 deaths that occurred in the CARVYKTI^® arm within the first 10 months of randomization, 10 deaths occurred prior to CARVYKTI^® infusion, and 19 deaths occurred after CARVYKTI^® infusion. Of the 10 deaths that occurred prior to CARVYKTI^® infusion, all occurred due to disease progression, and none occurred due to adverse events. Of the 19 deaths that occurred after CARVYKTI^® infusion, 3 occurred due to disease progression, and 16 occurred due to adverse events. The most common adverse events were due to infection (n=12).

Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with CARVYKTI^®. Among patients receiving CARVYKTI^® for RRMM in the CARTITUDE-1 & 4 studies (N=285), CRS occurred in 84% (238/285), including ≥Grade 3 CRS (ASCT 2019) in 4% (11/285) of patients. Median time to onset of CRS, any grade, was 7 days (range: 1 to 23 days). CRS resolved in 82% with a median duration of 4 days (range: 1 to 97 days). The most common manifestations of CRS in all patients combined (≥10%) included fever (84%), hypotension (29%) and aspartate aminotransferase increased (11%). Serious events that may be associated with CRS include pyrexia, hemophagocytic lymphohistiocytosis, respiratory failure, disseminated intravascular coagulation, capillary leak syndrome, and supraventricular and ventricular tachycardia. CRS occurred in 78% of patients in CARTITUDE-4 (3% Grade 3 to 4) and in 95% of patients in CARTITUDE-1 (4% Grade 3 to 4).

Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS.

Ensure that a minimum of two doses of tocilizumab are available prior to infusion of CARVYKTI^®.

Of the 285 patients who received CARVYKTI^® in clinical trials, 53% (150/285) patients received tocilizumab; 35% (100/285) received a single dose, while 18% (50/285) received more than 1 dose of tocilizumab. Overall, 14% (39/285) of patients received at least one dose of corticosteroids for treatment of CRS.

Monitor patients at least daily for 10 days following CARVYKTI^® infusion at a REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, immediately institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids.

Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.

Neurologic toxicities, which may be severe, life-threatening, or fatal, occurred following treatment with CARVYKTI^®. Neurologic toxicities included ICANS, neurologic toxicity with signs and symptoms of parkinsonism, GBS, immune mediated myelitis, peripheral neuropathies, and cranial nerve palsies. Counsel patients on the signs and symptoms of these neurologic toxicities, and on the delayed nature of onset of some of these toxicities. Instruct patients to seek immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time.

Among patients receiving CARVYKTI^® in the CARTITUDE-1 & 4 studies for RRMM, one or more neurologic toxicities occurred in 24% (69/285), including ≥Grade 3 cases in 7% (19/285) of patients. Median time to onset was 10 days (range: 1 to 101) with 63/69 (91%) of cases developing by 30 days. Neurologic toxicities resolved in 72% (50/69) of patients with a median duration to resolution of 23 days (range: 1 to 544). Of patients developing neurotoxicity, 96% (66/69) also developed CRS. Subtypes of neurologic toxicities included ICANS in 13%, peripheral neuropathy in 7%, cranial nerve palsy in 7%, parkinsonism in 3%, and immune mediated myelitis in 0.4% of the patients.

Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS): Patients receiving CARVYKTI^® may experience fatal or life-threatening ICANS following treatment with CARVYKTI^®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS.

Among patients receiving CARVYKTI^® in the CARTITUDE-1 & 4 studies, ICANS occurred in 13% (36/285), including Grade ≥3 in 2% (6/285) of the patients. Median time to onset of ICANS was 8 days (range: 1 to 28 days). ICANS resolved in 30 of 36 (83%) of patients with a median time to resolution of 3 days (range: 1 to 143 days). Median duration of ICANS was 6 days (range: 1 to 1229 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. Of patients with ICANS 97% (35/36) had CRS. The onset of ICANS occurred during CRS in 69% of patients, before and after the onset of CRS in 14% of patients respectively.

Immune Effector Cell-associated Neurotoxicity Syndrome occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3) and in 23% of patients in CARTITUDE-1 (3% Grade 3). The most frequent ≥2% manifestations of ICANS included encephalopathy (12%), aphasia (4%), headache (3%), motor dysfunction (3%), ataxia (2%) and sleep disorder (2%).

Monitor patients at least daily for 10 days following CARVYKTI^® infusion at the REMS-certified healthcare facility for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed.

Parkinsonism: Neurologic toxicity with parkinsonism has been reported in clinical trials of CARVYKTI^®. Among patients receiving CARVYKTI^® in the CARTITUDE-1 & 4 studies, parkinsonism occurred in 3% (8/285), including Grade ≥ 3 in 2% (5/285) of the patients. Median time to onset of parkinsonism was 56 days (range: 14 to 914 days). Parkinsonism resolved in 1 of 8 (13%) of patients with a median time to resolution of 523 days. Median duration of parkinsonism was 243.5 days (range: 62 to 720 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. The onset of parkinsonism occurred after CRS for all patients and after ICANS for 6 patients.

Parkinsonism occurred in 1% of patients in CARTITUDE-4 (no Grade 3 to 4) and in 6% of patients in CARTITUDE-1 (4% Grade 3 to 4).

Manifestations of parkinsonism included movement disorders, cognitive impairment, and personality changes. Monitor patients for signs and symptoms of parkinsonism that may be delayed in onset and managed with supportive care measures. There is limited efficacy information with medications used for the treatment of Parkinson’s disease for the improvement or resolution of parkinsonism symptoms following CARVYKTI^® treatment.

Guillain-Barré syndrome: A fatal outcome following GBS occurred following treatment with CARVYKTI^® despite treatment with intravenous immunoglobulins. Symptoms reported include those consistent with Miller-Fisher variant of GBS, encephalopathy, motor weakness, speech disturbances, and polyradiculoneuritis.

Monitor for GBS. Evaluate patients presenting with peripheral neuropathy for GBS. Consider treatment of GBS with supportive care measures and in conjunction with immunoglobulins and plasma exchange, depending on severity of GBS.

Immune mediated myelitis: Grade 3 myelitis occurred 25 days following treatment with CARVYKTI^® in CARTITUDE-4 in a patient who received CARVYKTI^® as subsequent therapy. Symptoms reported included hypoesthesia of the lower extremities and the lower abdomen with impaired sphincter control. Symptoms improved with the use of corticosteroids and intravenous immune globulin. Myelitis was ongoing at the time of death from other cause.

Peripheral neuropathy occurred following treatment with CARVYKTI^®. Among patients receiving CARVYKTI^® in the CARTITUDE-1 & 4 studies, peripheral neuropathy occurred in 7% (21/285), including Grade ≥3 in 1% (3/285) of the patients. Median time to onset of peripheral neuropathy was 57 days (range: 1 to 914 days). Peripheral neuropathy resolved in 11 of 21 (52%) of patients with a median time to resolution of 58 days (range: 1 to 215 days). Median duration of peripheral neuropathy was 149.5 days (range: 1 to 692 days) in all patients including those with ongoing neurologic events at the time of death or data cut off.

Peripheral neuropathies occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3 to 4) and in 7% of patients in CARTITUDE-1 (2% Grade 3 to 4). Monitor patients for signs and symptoms of peripheral neuropathies. Patients who experience peripheral neuropathy may also experience cranial nerve palsies or GBS.

Cranial nerve palsies occurred following treatment with CARVYKTI^®. Among patients receiving CARVYKTI^® in the CARTITUDE-1 & 4 studies, cranial nerve palsies occurred in 7% (19/285), including Grade ≥3 in 1% (1/285) of the patients. Median time to onset of cranial nerve palsies was 21 days (range: 17 to 101 days). Cranial nerve palsies resolved in 17 of 19 (89%) of patients with a median time to resolution of 66 days (range: 1 to 209 days). Median duration of cranial nerve palsies was 70 days (range: 1 to 262 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. Cranial nerve palsies occurred in 9% of patients in CARTITUDE-4 (1% Grade 3 to 4) and in 3% of patients in CARTITUDE-1 (1% Grade 3 to 4).

The most frequent cranial nerve affected was the 7th cranial nerve. Additionally, cranial nerves III, V, and VI have been reported to be affected.

Monitor patients for signs and symptoms of cranial nerve palsies. Consider management with systemic corticosteroids, depending on the severity and progression of signs and symptoms.

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): Among patients receiving CARVYKTI^® in the CARTITUDE-1 & 4 studies, HLH/MAS occurred in 1% (3/285) of patients. All events of HLH/MAS had onset within 99 days of receiving CARVYKTI^®, with a median onset of 10 days (range: 8 to 99 days) and all occurred in the setting of ongoing or worsening CRS. The manifestations of HLH/MAS included hyperferritinemia, hypotension, hypoxia with diffuse alveolar damage, coagulopathy and hemorrhage, cytopenia and multi-organ dysfunction, including renal dysfunction and respiratory failure.

Patients who develop HLH/MAS have an increased risk of severe bleeding. Monitor hematologic parameters in patients with HLH/MAS and transfuse per institutional guidelines. Fatal cases of HLH/MAS occurred following treatment with CARVYKTI^®.
HLH is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of HLH/MAS should be administered per institutional standards.

CARVYKTI^® REMS: Because of the risk of CRS and neurologic toxicities, CARVYKTI^® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI^® REMS.

Further information is available at https://www.carvyktirems.com/ or 1-844-672-0067.

Prolonged and Recurrent Cytopenias: Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI^® infusion.

Among patients receiving CARVYKTI^® in the CARTITUDE-1 & 4 studies, Grade 3 or higher cytopenias not resolved by day 30 following CARVYKTI^® infusion occurred in 62% (176/285) of the patients and included thrombocytopenia 33% (94/285), neutropenia 27% (76/285), lymphopenia 24% (67/285) and anemia 2% (6/285). After Day 60 following CARVYKTI^® infusion 22%, 20%, 5%, and 6% of patients had a recurrence of Grade 3 or 4 lymphopenia, neutropenia, thrombocytopenia, and anemia respectively, after initial recovery of their Grade 3 or 4 cytopenia. Seventy-seven percent (219/285) of patients had one, two or three or more recurrences of Grade 3 or 4 cytopenias after initial recovery of Grade 3 or 4 cytopenia. Sixteen and 25 patients had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the time of death.

Monitor blood counts prior to and after CARVYKTI^® infusion. Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines.

Infections: CARVYKTI^® should not be administered to patients with active infection or inflammatory disorders. Severe, life-threatening, or fatal infections, occurred in patients after CARVYKTI^® infusion.

Among patients receiving CARVYKTI^® in the CARTITUDE-1 & 4 studies, infections occurred in 57% (163/285), including ≥Grade 3 in 24% (69/285) of patients. Grade 3 or 4 infections with an unspecified pathogen occurred in 12%, viral infections in 6%, bacterial infections in 5%, and fungal infections in 1% of patients. Overall, 5% (13/285) of patients had Grade 5 infections, 2.5% of which were due to COVID-19. Patients treated with CARVYKTI^® had an increased rate of fatal COVID-19 infections compared to the standard therapy arm.

Monitor patients for signs and symptoms of infection before and after CARVYKTI^® infusion and treat patients appropriately. Administer prophylactic, pre-emptive and/or therapeutic antimicrobials according to the standard institutional guidelines. Febrile neutropenia was observed in 5% of patients after CARVYKTI^® infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids and other supportive care, as medically indicated. Counsel patients on the importance of prevention measures. Follow institutional guidelines for the vaccination and management of immunocompromised patients with COVID-19.

Viral Reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients with hypogammaglobulinemia. Perform screening for Cytomegalovirus (CMV), HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) or any other infectious agents if clinically indicated in accordance with clinical guidelines before collection of cells for manufacturing. Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice.

Hypogammaglobulinemia: can occur in patients receiving treatment with CARVYKTI^®. Among patients receiving CARVYKTI^® in the CARTITUDE-1 & 4 studies, hypogammaglobulinemia adverse event was reported in 36% (102/285) of patients; laboratory IgG levels fell below 500mg/dl after infusion in 93% (265/285) of patients. Hypogammaglobulinemia either as an adverse reaction or laboratory IgG level below 500mg/dl, after infusion occurred in 94% (267/285) of patients treated. Fifty six percent (161/285) of patients received intravenous immunoglobulin (IVIG) post CARVYKTI^® for either an adverse reaction or prophylaxis.
Monitor immunoglobulin levels after treatment with CARVYKTI^® and administer IVIG for IgG <400 mg/dL. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

Use of Live Vaccines: The safety of immunization with live viral vaccines during or following CARVYKTI^® treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during CARVYKTI^® treatment, and until immune recovery following treatment with CARVYKTI^®.

Hypersensitivity Reactions occurred following treatment with CARVYKTI^®. Among patients receiving CARVYKTI^® in the CARTITUDE-1 & 4 studies, hypersensitivity reactions occurred in 5% (13/285), all of which were ≤Grade 2. Manifestations of hypersensitivity reactions included flushing, chest discomfort, tachycardia, wheezing, tremor, burning sensation, non-cardiac chest pain, and pyrexia.

Serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) in CARVYKTI^®. Patients should be carefully monitored for 2 hours after infusion for signs and symptoms of severe reaction. Treat promptly and manage patients appropriately according to the severity of the hypersensitivity reaction.

Secondary Malignancies: Patients treated with CARVYKTI^® may develop secondary malignancies. Among patients receiving CARVYKTI^® in the CARTITUDE-1 & 4 studies, myeloid neoplasms occurred in 5% (13/285) of patients (9 cases of myelodysplastic syndrome, 3 cases of acute myeloid leukemia, and 1 case of myelodysplastic syndrome followed by acute myeloid leukemia). The median time to onset of myeloid neoplasms was 447 days (range: 56 to 870 days) after treatment with CARVYKTI^®. Ten of these 13 patients died following the development of myeloid neoplasms; 2 of the 13 cases of myeloid neoplasm occurred after initiation of subsequent antimyeloma therapy. Cases of myelodysplastic syndrome and acute myeloid leukemia have also been reported in the post marketing setting. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI^®. Mature T-cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusions, and may include fatal outcomes.

Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Janssen Biotech, Inc. at 1-800-526-7736 for reporting and to obtain instructions on collection of patient samples.

Effects on Ability to Drive and Use Machines: Due to the potential for neurologic events, including altered mental status, seizures, neurocognitive decline or neuropathy, patients receiving CARVYKTI^® are at risk for altered or decreased consciousness or coordination in the 8 weeks following CARVYKTI^® infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery during this initial period, and in the event of new onset of any neurologic toxicities.

ADVERSE REACTIONS

The most common nonlaboratory adverse reactions (incidence greater than 20%) are pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections-pathogen unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting. The most common Grade 3 or 4 laboratory adverse reactions (incidence greater than or equal to 50%) include lymphopenia, neutropenia, white blood cell decreased, thrombocytopenia, and anemia.

Please read full Prescribing Information, including Boxed Warning, for CARVYKTI^®.

DARZALEX FASPRO^® INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS
DARZALEX FASPRO^® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:

• In combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant
• In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
• In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
• In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
• In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor (PI)
• In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
• In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
• As monotherapy in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

DARZALEX FASPRO^® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Hypersensitivity and Other Administration Reactions
Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO^®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO^®.

Systemic Reactions
In a pooled safety population of 1249 patients with multiple myeloma (N=1056) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or in combination, 7% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 0.7%, Grade 4: 0.1%). Systemic administration-related reactions occurred in 7% of patients with the first injection, 0.2% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 2.9 hours (range: 5 minutes to 3.5 days). Of the 165 systemic administration-related reactions that occurred in 93 patients, 144 (87%) occurred on the day of DARZALEX FASPRO^® administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.

Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.

Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO^®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO^® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.

Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO^® and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO^®.

Local Reactions
In this pooled safety population, injection-site reactions occurred in 7% of patients, including Grade 2 reactions in 0.8%. The most frequent (>1%) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO^®. Monitor for local reactions and consider symptomatic management.

Neutropenia
Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO^® until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO^®, higher rates of Grade 3-4 neutropenia were observed.

Thrombocytopenia
Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX FASPRO^® until recovery of platelets.

Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX FASPRO^® can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO^® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO^® and for 3 months after the last dose.

The combination of DARZALEX FASPRO^® with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.

Interference With Serological Testing
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted.

Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO^®. Type and screen patients prior to starting DARZALEX FASPRO^®.

Interference With Determination of Complete Response
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO^®-treated patients with IgG kappa myeloma protein.

ADVERSE REACTIONS

In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO^® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral sensory neuropathy, constipation, pneumonia, and peripheral edema.

The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO^® are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.

Please click here to see the full Prescribing Information for DARZALEX FASPRO^®.

DARZALEX^® INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS
DARZALEX^® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:

· In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
· In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
· In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
· In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor
· In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
· In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
· As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent

CONTRAINDICATIONS

DARZALEX^® is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions

DARZALEX^® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be lifethreatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX^®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension and blurred vision.

When DARZALEX^® dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX^®, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX^® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.

Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX^® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX^® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.

To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX^® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.

Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX infusion. If ocular symptoms occur, interrupt DARZALEX infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX.

Interference With Serological Testing

Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX^®. Type and screen patients prior to starting DARZALEX^®.

Neutropenia and Thrombocytopenia

DARZALEX^® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX^® until recovery of neutrophils or for recovery of platelets.

Interference With Determination of Complete Response

Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.

Embryo-Fetal Toxicity

Based on the mechanism of action, DARZALEX^® can cause fetal harm when administered to a pregnant woman. DARZALEX^® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX^® and for 3 months after the last dose.

The combination of DARZALEX^® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.

ADVERSE REACTIONS

The most frequently reported adverse reactions (incidence ≥20%) were: upper respiratory infection, neutropenia, infusionrelated reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX^® are: neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.

Please click here to see the full Prescribing Information.

IMBRUVICA^® IMPORTANT SAFETY INFORMATION

INDICATIONS

IMBRUVICA^® is a kinase inhibitor indicated for the treatment of:

· Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL).
· Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion.
· Adult patients with Waldenström’s macroglobulinemia (WM).
· Adult and pediatric patients age 1 year and older with chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy.

For more information, visit www.IMBRUVICA.com.

WARNINGS AND PRECAUTIONS

Hemorrhage: Fatal bleeding events have occurred in patients who received IMBRUVICA ^®. Major hemorrhage (≥ Grade 3, serious, or any central nervous system events; e.g., intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post procedural hemorrhage) occurred in 4.2% of patients, with fatalities occurring in 0.4% of 2,838 patients who received IMBRUVICA ^® in 27 clinical trials. Bleeding events of any grade including bruising and petechiae occurred in 39%, and excluding bruising and petechiae occurred in 23% of patients who received IMBRUVICA®, respectively.

The mechanism for the bleeding events is not well understood.

Use of either anticoagulant or antiplatelet agents concomitantly with IMBRUVICA^® increases the risk of major hemorrhage. Across clinical trials, 3.1% of 2,838 patients who received IMBRUVICA^® without antiplatelet or anticoagulant therapy experienced major hemorrhage. The addition of antiplatelet therapy with or without anticoagulant therapy increased this percentage to 4.4%, and the addition of anticoagulant therapy with or without antiplatelet therapy increased this percentage to 6.1%. Consider the risks and benefits of anticoagulant or antiplatelet therapy when co-administered with IMBRUVICA^®. Monitor for signs and symptoms of bleeding.

Consider the benefit-risk of withholding IMBRUVICA^® for at least 3 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA^® therapy. Grade 3 or greater infections occurred in 21% of 1,476 patients with B-cell malignancies who received IMBRUVICA^® in clinical trials. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA®. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections. Monitor and evaluate patients for fever and infections and treat appropriately.

Cardiac Arrhythmias, Cardiac Failure, and Sudden Death: Fatal and serious cardiac arrhythmias and cardiac failure have occurred with IMBRUVICA^®. Deaths due to cardiac causes or sudden deaths occurred in 1% of 4,896 patients who received IMBRUVICA^® in clinical trials, including in patients who received IMBRUVICA^® in unapproved monotherapy or combination regimens. These adverse reactions occurred in patients with and without preexisting hypertension or cardiac comorbidities. Patients with cardiac comorbidities may be at greater risk of these events.

Grade 3 or greater ventricular tachyarrhythmias were reported in 0.2%, Grade 3 or greater atrial fibrillation and atrial flutter were reported in 3.7%, and Grade 3 or greater cardiac failure was reported in 1.3% of 4,896 patients who received IMBRUVICA^® in clinical trials, including in patients who received IMBRUVICA^® in unapproved monotherapy or combination regimens. These events have occurred particularly in patients with cardiac risk factors including hypertension and diabetes mellitus, a previous history of cardiac arrhythmias, and in patients with acute infections.

Evaluate cardiac history and function at baseline, and monitor patients for cardiac arrhythmias and cardiac function. Obtain further evaluation (e.g., ECG, echocardiogram) as indicated for patients who develop symptoms of arrhythmia (e.g., palpitations, lightheadedness, syncope, chest pain), new onset dyspnea, or other cardiovascular concerns. Manage cardiac arrhythmias and cardiac failure appropriately, follow dose modification guidelines, and consider the risks and benefits of continued IMBRUVICA^® treatment.

Hypertension: Hypertension occurred in 19% of 1,476 patients with B-cell malignancies who received IMBRUVICA® in clinical trials. Grade 3 or greater hypertension occurred in 8% of patients. Based on data from a subset of these patients, (N=1,124), the median time to onset was 5.9 months (range, 0 to 24 months). In a long-term safety analysis over 5 years of 1,284 patients with B-cell malignancies treated for a median of 36 months (range, 0 to 98 months), the cumulative rate of hypertension increased over time. The prevalence for Grade 3 or greater hypertension was 4% (year 0-1), 7% (year 1-2), 9% (year 2-3), 9% (year 3-4), and 9% (year 4-5); the overall incidence for the 5-year period was 11%. Monitor blood pressure in patients treated with IMBRUVICA^®, initiate or adjust anti-hypertensive medication throughout treatment with IMBRUVICA^® as appropriate, and follow dosage modification guidelines for Grade 3 or higher hypertension.

Cytopenias: In 645 patients with B-cell malignancies who received IMBRUVICA^® as a single agent, grade 3 or 4 neutropenia occurred in 23% of patients, grade 3 or 4 thrombocytopenia in 8% and grade 3 or 4 anemia in 2.8%, based on laboratory measurements. Monitor complete blood counts monthly.

Second Primary Malignancies: Other malignancies (10%), including non-skin carcinomas (3.9%), occurred among the 1,476 patients with B-cell malignancies who received IMBRUVICA^® in clinical trials. The most frequent second primary malignancy was non-melanoma skin cancer (6%).

Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported with IMBRUVICA^®. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA^® can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMBRUVICA® and for 1 month after the last dose. Advise males with female partners of reproductive potential to use effective contraception during the same time period.

ADVERSE REACTIONS

B-cell malignancies: The most common adverse reactions (≥30%) in adult patients with B-cell malignancies were thrombocytopenia (55%)*, diarrhea (44%), fatigue (39%), musculoskeletal pain (39%), neutropenia (39%)*, rash (36%), anemia (35%)*, bruising (32%), and nausea (30%).

The most common Grade ≥ 3 adverse reactions (≥5%) in adult patients with B-cell malignancies were neutropenia (21%)*, thrombocytopenia (14%)*, pneumonia (8%), and hypertension (8%).

Approximately 9% (CLL/SLL), and 14% (WM) of adult patients had a dose reduction due to adverse reactions. Approximately 4-10% (CLL/SLL) and 5% (WM) of adult patients discontinued due to adverse reactions.

cGVHD: The most common adverse reactions (≥20%) in adult or pediatric patients with cGVHD were fatigue (57%), anemia (49%)*, bruising (40%), diarrhea (36%), thrombocytopenia (33%)*, musculoskeletal pain (30%), pyrexia (30%), muscle spasms (29%), stomatitis (29%), hemorrhage (26%), nausea (26%), abdominal pain (23%), pneumonia (23%), and headache (21%).

The most common Grade 3 or higher adverse reactions (≥5%) reported in adult or pediatric patients with cGVHD were pneumonia (14%), anemia (13%)*, fatigue (12%), pyrexia (11%), diarrhea (10%), neutropenia (10%)*, sepsis (10%), osteonecrosis (9%), stomatitis (9%), hypokalemia (7%), headache (5%), and musculoskeletal pain (5%).

Discontinuation of IMBRUVICA^® treatment due to an adverse reaction occurred in 24% of adult patients and 23% of pediatric patients. Adverse reactions leading to dose reduction occurred in 26% of adult patients and 19% of pediatric patients.

*Treatment-emergent decreases (all grades) were based on laboratory measurements.

DRUG INTERACTIONS

CYP3A Inhibitors: Co-administration of IMBRUVICA^® with strong or moderate CYP3A inhibitors may increase ibrutinib plasma concentrations. Increased ibrutinib concentrations may increase the risk of drug-related toxicity. Dose modifications of IMBRUVICA® are recommended when used concomitantly with posaconazole, voriconazole, and moderate CYP3A inhibitors. Avoid concomitant use of other strong CYP3A inhibitors. Interrupt IMBRUVICA^® if strong inhibitors are used short-term (e.g., for ≤ 7 days). Avoid grapefruit and Seville oranges during IMBRUVICA® treatment, as these contain strong or moderate inhibitors of CYP3A. See dose modification guidelines in USPI sections 2.3 and 7.1.

CYP3A Inducers: Avoid coadministration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Pediatric Use: The safety and effectiveness of IMBRUVICA^® have not been established for the treatment of cGVHD after failure of one or more lines of therapy in pediatric patients less than 1 year of age. The safety and effectiveness of IMBRUVICA^® in pediatric patients have not been established in CLL/SLL, CLL/SLL with 17p deletion, WM, or in patients with mature B-cell non-Hodgkin lymphoma.

In the randomized population from a study that included 35 patients (26 pediatric patients age 5 to less than 17 years) with previously treated mature B-cell non-Hodgkin lymphoma, major hemorrhage and discontinuation of chemoimmunotherapy due to adverse reactions occurred more frequently in the ibrutinib plus chemoimmunotherapy arm compared to the chemoimmunotherapy alone arm.

Hepatic Impairment:
Adult Patients with B-cell Malignancies: Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA^® in patients with severe hepatic impairment. In patients with mild or moderate impairment, reduce recommended IMBRUVICA® dose and monitor more frequently for adverse reactions of IMBRUVICA^®.

Patients with cGVHD: Avoid use of IMBRUVICA^® in patients with total bilirubin level > 3x upper limit of normal (ULN) (unless of non-hepatic origin or due to Gilbert’s syndrome). Reduce recommended dose when administering IMBRUVICA® to patients with total bilirubin level > 1.5 to 3x ULN (unless of non-hepatic origin or due to Gilbert’s syndrome).

Please click here to see the full Prescribing Information.

TALVEY^® IMPORTANT SAFETY INFORMATION

INDICATION AND USAGE

TALVEY^® (talquetamab-tgvs) is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY, including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TALVEY^®. Initiate TALVEY® treatment with step-up dosing to reduce the risk of CRS. Withhold TALVEY^® until CRS resolves or permanently discontinue based on severity.

Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), and serious and life-threatening or fatal reactions, can occur with TALVEY®. Monitor patients for signs and symptoms of neurologic toxicity including ICANS during treatment. Withhold or discontinue TALVEY^® based on severity.

Because of the risk of CRS and neurologic toxicity, including ICANS, TALVEY^® is available only through a restricted program called the TECVAYLI^® and TALVEY^® Risk Evaluation and Mitigation Strategy (REMS).
CONTRAINDICATIONS: None.

WARNINGS AND PRECAUTIONS

Cytokine Release Syndrome (CRS): TALVEY^® can cause cytokine release syndrome, including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 76% of patients who received TALVEY^® at the recommended dosages, with Grade 1 CRS occurring in 57% of patients, Grade 2 in 17%, and Grade 3 in 1.5%. Recurrent CRS occurred in 30% of patients. CRS occurred in 33% of patients with step-up dose 3 in the biweekly dosing schedule (N=153). CRS occurred in 30% of patients with the first 0.4 mg/kg treatment dose and in 12% of patients treated with the first 0.8 mg/kg treatment dose. The CRS rate for both dosing schedules combined was less than 3% for each of the remaining doses in Cycle 1 and less than 3% cumulatively from Cycle 2 onward. The median time to onset of CRS was 27 (range: 0.1 to 167) hours from the last dose, and the median duration was 17 (range: 0 to 622) hours. Clinical signs and symptoms of CRS include but are not limited to pyrexia, hypotension, chills, hypoxia, headache, and tachycardia. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).

Initiate therapy with step-up dosing and administer pre-treatment medications (corticosteroids, antihistamine, and antipyretics) prior to each dose of TALVEY^® in the step-up dosing schedule to reduce the risk of CRS. Monitor patients following administration accordingly. In patients who experience CRS, pre-treatment medications should be administered prior to the next TALVEY^® dose.

Counsel patients to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care based on severity, and consider further management per current practice guidelines. Withhold TALVEY^® until CRS resolves or permanently discontinue based on severity.

Neurologic Toxicity including ICANS: TALVEY® can cause serious or life-threatening neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including fatal reactions. In the clinical trial, neurologic toxicity occurred in 55% of patients who received the recommended dosages, with Grade 3 or 4 neurologic toxicity occurring in 6% of patients. The most frequent neurologic toxicities were headache (20%), encephalopathy (15%), sensory neuropathy (14%), and motor dysfunction (10%).

ICANS was reported in 9% of 265 patients where ICANS was collected and who received the recommended dosages. Recurrent ICANS occurred in 3% of patients. Most patients experienced ICANS following step-up dose 1 (3%), step-up dose 2 (3%), step-up dose 3 of the biweekly dosing schedule (1.8%), or the initial treatment dose of the weekly dosing schedule (2.6%) (N=156) or the biweekly dosing schedule (3.7%) (N=109). The median time to onset of ICANS was 2.5 (range: 1 to 16) days after the most recent dose with a median duration of 2 (range: 1 to 22) days. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy, and bradyphrenia.

Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate the patient and provide supportive care based on severity; withhold or permanently discontinue TALVEY® based on severity and consider further management per current practice guidelines. [see Dosage and Administration (2.5)].

Due to the potential for neurologic toxicity, patients receiving TALVEY^® are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during the step-up dosing schedule and for 48 hours after completion of the step-up dosing schedule, and in the event of new onset of any neurological symptoms, until symptoms resolve.

TECVAYLI^® and TALVEY^® REMS: TALVEY^® is available only through a restricted program under a REMS, called the TECVAYLI^® and TALVEY^® REMS because of the risks of CRS and neurologic toxicity, including ICANS.

Further information about the TECVAYLI^® and TALVEY^® REMS program is available at www.TEC-TALREMS.com or by telephone at 1-855-810-8064.

Oral Toxicity and Weight Loss: TALVEY^® can cause oral toxicities, including dysgeusia, dry mouth, dysphagia, and stomatitis. In the clinical trial, 80% of patients had oral toxicity, with Grade 3 occurring in 2.1% of patients who received the recommended dosages. The most frequent oral toxicities were dysgeusia (49%), dry mouth (34%), dysphagia (23%), and ageusia (18%). The median time to onset of oral toxicity was 15 (range: 1 to 634) days, and the median time to resolution to baseline was 43 (1 to 530) days. Oral toxicity did not resolve to baseline in 65% of patients.

TALVEY^® can cause weight loss. In the clinical trial, 62% of patients experienced weight loss of 5% or greater, regardless of having an oral toxicity, including 28% of patients with Grade 2 (10% or greater) weight loss and 2.7% of patients with Grade 3 (20% or greater) weight loss. The median time to onset of Grade 2 or higher weight loss was 67 (range: 6 to 407) days, and the median time to resolution was 50 (range: 1 to 403) days. Weight loss did not resolve in 57% of patients who reported weight loss.

Monitor patients for signs and symptoms of oral toxicity. Counsel patients to seek medical attention should signs or symptoms of oral toxicity occur and provide supportive care as per current clinical practice, including consultation with a nutritionist. Monitor weight regularly during therapy. Evaluate clinically significant weight loss further. Withhold TALVEY^® or permanently discontinue based on severity.

Infections: TALVEY^® can cause infections, including life-threatening or fatal infections.Serious infections occurred in 16% of patients, with fatal infections in 1.5% of patients. Grade 3 or 4 infections occurred in 17% of patients. The most common serious infections reported were bacterial infection (8%), which included sepsis and COVID-19 (2.7%).

Monitor patients for signs and symptoms of infection prior to and during treatment with TALVEY^® and treat appropriately. Administer prophylactic antimicrobials according to local guidelines. Withhold or consider permanently discontinuing TALVEY^® as recommended, based on severity.

Cytopenias: TALVEY^® can cause cytopenias, including neutropenia and thrombocytopenia. In the clinical trial, Grade 3 or 4 decreased neutrophils occurred in 35% of patients, and Grade 3 or 4 decreased platelets occurred in 22% of patients who received TALVEY^®. The median time to onset for Grade 3 or 4 neutropenia was 22 (range: 1 to 312) days, and the median time to resolution to Grade 2 or lower was 8 (range: 1 to 79) days. The median time to onset for Grade 3 or 4 thrombocytopenia was 12 (range: 2 to 183) days, and the median time to resolution to Grade 2 or lower was 10 (range: 1 to 64) days. Monitor complete blood counts during treatment and withhold TALVEY^® as recommended, based on severity.

Skin Toxicity: TALVEY^® can cause serious skin reactions, including rash, maculo-papular rash, erythema, and erythematous rash. In the clinical trial, skin reactions occurred in 62% of patients, with grade 3 skin reactions in 0.3%. The median time to onset was 25 (range: 1 to 630) days. The median time to improvement to grade 1 or less was 33 days.

Monitor for skin toxicity, including rash progression. Consider early intervention and treatment to manage skin toxicity.Withhold TALVEY^® as recommended based on severity.

Hepatotoxicity: TALVEY^® can cause hepatotoxicity. Elevated ALT occurred in 33% of patients, with grade 3 or 4 ALT elevation occurring in 2.7%; elevated AST occurred in 31% of patients, with grade 3 or 4 AST elevation occurring in 3.3%. Grade 3 or 4 elevations of total bilirubin occurred in 0.3% of patients. Liver enzyme elevation can occur with or without concurrent CRS.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TALVEY^® or consider permanent discontinuation of TALVEY^®, based on severity [see Dosage and Administration (2.5)].

Embryo-Fetal Toxicity: Based on its mechanism of action, TALVEY^® may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TALVEY^® and for 3 months after the last dose.

Adverse Reactions: The most common adverse reactions (≥20%) are pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decreased, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache.

The most common Grade 3 or 4 laboratory abnormalities (≥30%) are lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased.

Please read full Prescribing Information, including Boxed Warning, for TALVEY^®.

TECVAYLI^® IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TECVAYLI^®. Initiate treatment with TECVAYLI^® step-up dosing schedule to reduce risk of CRS. Withhold TECVAYLI^® until CRS resolves or permanently discontinue based on severity.

Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious and life-threatening reactions, can occur in patients receiving TECVAYLI^®. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI^® until neurologic toxicity resolves or permanently discontinue based on severity.

TECVAYLI^® is available only through a restricted program called the TECVAYLI^® and TALVEY^® Risk Evaluation and Mitigation Strategy (REMS).

INDICATION AND USAGE

TECVAYLI^® (teclistamab-cqyv) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.

This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

WARNINGS AND PRECAUTIONS

Cytokine Release Syndrome - TECVAYLI^® can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 72% of patients who received TECVAYLI^® at the recommended dose, with Grade 1 CRS occurring in 50% of patients, Grade 2 in 21%, and Grade 3 in 0.6%. Recurrent CRS occurred in 33% of patients. Most patients experienced CRS following step-up dose 1 (42%), step-up dose 2 (35%), or the initial treatment dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI^®. The median time to onset of CRS was 2 (range: 1 to 6) days after the most recent dose with a median duration of 2 (range: 1 to 9) days. Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation).

Initiate therapy according to TECVAYLI^® step-up dosing schedule to reduce risk of CRS. Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI^® accordingly. At the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold or permanently discontinue TECVAYLI^® based on severity.

TECVAYLI^® is available only through a restricted program under a REMS.

Neurologic Toxicity including ICANS - TECVAYLI^® can cause serious or life-threatening neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

In the clinical trial, neurologic toxicity occurred in 57% of patients who received TECVAYLI^® at the recommended dose, with Grade 3 or 4 neurologic toxicity occurring in 2.4% of patients. The most frequent neurologic toxicities were headache (25%), motor dysfunction (16%), sensory neuropathy (15%), and encephalopathy (13%). With longer follow-up, Grade 4 seizure and fatal Guillain-Barré syndrome (one patient each) occurred in patients who received TECVAYLI^®.

In the clinical trial, ICANS was reported in 6% of patients who received TECVAYLI^® at the recommended dose. Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent doses of TECVAYLI^®. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.

Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or permanently discontinue TECVAYLI^® based on severity per recommendations and consider further management per current practice guidelines.

Due to the potential for neurologic toxicity, patients are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI^® step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves.

TECVAYLI^® is available only through a restricted program under a REMS.

TECVAYLI^® and TALVEY^® REMS - TECVAYLI^® is available only through a restricted program under a REMS called the TECVAYLI^® and TALVEY^® REMS because of the risks of CRS and neurologic toxicity, including ICANS.

Hepatotoxicity - TECVAYLI^® can cause hepatotoxicity, including fatalities. In patients who received TECVAYLI^® at the recommended dose in the clinical trial, there was one fatal case of hepatic failure. Elevated aspartate aminotransferase (AST) occurred in 34% of patients, with Grade 3 or 4 elevations in 1.2%. Elevated alanine aminotransferase (ALT) occurred in 28% of patients, with Grade 3 or 4 elevations in 1.8%. Elevated total bilirubin occurred in 6% of patients with Grade 3 or 4 elevations in 0.6%. Liver enzyme elevation can occur with or without concurrent CRS.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI^® or consider permanent discontinuation of TECVAYLI^® based on severity.

Infections - TECVAYLI^® can cause severe, life-threatening, or fatal infections. In patients who received TECVAYLI^® at the recommended dose in the clinical trial, serious infections, including opportunistic infections, occurred in 30% of patients, with Grade 3 or 4 infections in 35%, and fatal infections in 4.2%.

Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI^® and treat appropriately. Administer prophylactic antimicrobials according to guidelines. Withhold TECVAYLI^® or consider permanent discontinuation of TECVAYLI^® based on severity.

Monitor immunoglobulin levels during treatment with TECVAYLI^® and treat according to guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

Neutropenia - TECVAYLI^® can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI^® at the recommended dose in the clinical trial, decreased neutrophils occurred in 84% of patients, with Grade 3 or 4 decreased neutrophils in 56%. Febrile neutropenia occurred in 3% of patients.

Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines. Monitor patients with neutropenia for signs of infection. Withhold TECVAYLI^® based on severity.

Hypersensitivity and Other Administration Reactions - TECVAYLI^® can cause both systemic administration-related and local injection-site reactions. Systemic Reactions - In patients who received TECVAYLI^® at the recommended dose in the clinical trial, 1.2% of patients experienced systemic-administration reactions, which included Grade 1 recurrent pyrexia and Grade 1 swollen tongue. Local Reactions - In patients who received TECVAYLI^® at the recommended dose in the clinical trial, injection-site reactions occurred in 35% of patients, with Grade 1 injection-site reactions in 30% and Grade 2 in 4.8%. Withhold TECVAYLI^® or consider permanent discontinuation of TECVAYLI^® based on severity.

Embryo-Fetal Toxicity - Based on its mechanism of action, TECVAYLI^® may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI^® and for 5 months after the last dose.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.

Please read full Prescribing Information, including Boxed WARNING, for TECVAYLI^®.

About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.innovativemedicine.jnj.com. Follow us at @JNJInnovMed. Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen Global Services, LLC and Janssen Scientific Affairs, LLC are Johnson & Johnson companies.

Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of RYBREVANT^® (amivantamab-vmjw), LAZCLUZE™ (lazertinib), AKEEGA^® (niraparib), CARVYKTI^® (ciltacabtagene autoleucel), DARZALEX^® (daratumumab), DARZALEX FASPRO^® (daratumumab and hyaluronidase-fihj), IMBRUVICA^® (ibrutinib), TALVEY^® (talquetamab-tgvs) and TECVAYLI^® (teclistamab-cqyv). The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s most recent Annual Report on Form 10-K, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments.

Footnotes
^†See the NCCN Guidelines for detailed recommendations, including other treatment options.^‡The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories.^§The NCCN Content does not constitute medical advice and should not be used in place of seeking professional medical advice, diagnosis or treatment by licensed practitioners. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

¹ AKEEGA^® U.S. Prescribing Information.

² RYBREVANT^® Prescribing Information. Horsham, PA: Janssen Biotech, Inc.

³ Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Non-Small Cell Lung Cancer V.3.2025 © National Comprehensive Cancer Network, Inc. All rights reserved. To view the most recent and complete version of the guideline, go online to NCCN.org. Accessed March 2025.

⁴ Cho BC, et al. Lazertinib versus gefitinib as first-line treatment in patients with EGFR-mutated advanced non-small-cell lung cancer: results from LASER301. J Clin Oncol. 2023;41(26):4208-4217.

⁵ CARVYKTI^® U.S. Prescribing Information.

⁶ DARZALEX FASPRO^® U.S. Prescribing Information.

⁷ DARZALEX^® U.S. Prescribing Information.

⁸ Genetics Home Reference. Isolated growth hormone deficiency. http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.

⁹ Turetsky A, et al. Single cell imaging of Bruton’s tyrosine kinase using an irreversible inhibitor. Scientific Reports. 2014;6:4782.

¹⁰ de Rooij MF, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012;119(11):2590-2594.

¹¹ IMBRUVICA^® U.S. Prescribing Information, February 2024.

¹² TALVEY^® U.S. Prescribing Information, August 2023.

¹³ European Medicines Agency. TALVEY Summary of Product Characteristics. August 2023.

¹⁴ U.S. FDA Approves TECVAYLI^® (teclistamab-cqyv), the First Bispecific T-cell Engager Antibody for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma. https://www.jnj.com/u-s-fda-approves-tecvayli-teclistamab-cqyv-the-first-bispecific-t-cell-engager-antibody-for-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma. Accessed May 2025.