Bristol Myers Squibb Presents New Research at ASCO and EHA 2021 Featuring Novel Approaches and Demonstrating Significant Progress to Improve Survival in Cancer and Blood Disorders

Bristol Myers Squibb (NYSE: BMY) today announced the presentation of research demonstrating the potential of its medicines to deliver long-term survival, improve outcomes and address areas of high unmet need across cancers and blood disorders at the 2021 American Society of Clinical Oncology (ASCO) Virtual Annual Meeting, June 4-8, and the European Hematology Association (EHA) 2021 Virtual Congress, June 9-17. Data from more than 75 company-sponsored studies, investigator-sponsored studies and collaborations evaluating compounds across 18 cancer types and blood disorders will be featured at the two meetings, including two abstracts (Abstract #9503 and #LBA4001) selected for the official ASCO press program and one (Abstract #S101) for the EHA presidential symposium.

“Our breadth of data at this year’s ASCO and EHA meetings highlights our diverse pipeline, with numerous approaches aimed at addressing the underlying biology of cancer and blood disorders,” said Samit Hirawat, M.D., executive vice president, chief medical officer, Global Drug Development, Bristol Myers Squibb. “Through our comprehensive research programs, we’re exploring how immunotherapy combinations may improve survival outcomes for patients with cancer, leading significant advances in cell therapy and erythroid maturation and building on decades of experience in protein degradation to evaluate more potent agents. As we make progress in developing new therapies, we recognize that the needs of patients extend beyond treatment, and we are committed to supporting all aspects of care for all patients. In collaboration with the community, we're working to improve survivorship support and to advance health equity in a time when disparities in care have become an even more pressing issue."

Key data being presented by Bristol Myers Squibb at ASCO and EHA 2021 include:

Solid Tumor

• First presentation of results from the RELATIVITY-047 trial evaluating the LAG-3 blocking antibody relatlimab, the company’s third distinct checkpoint inhibitor and latest innovation, demonstrating clinical benefit for patients in a fixed-dose combination with nivolumab. These data are part of the official ASCO press program on May 14, 2021.
• Longest-ever survival data of the Opdivo (nivolumab) plus Yervoy (ipilimumab) combination from CheckMate -067, demonstrating durable survival benefits over 6.5 years in patients with advanced or metastatic melanoma.
• First disclosure of data from CheckMate -648 showcasing survival benefits of Opdivo plus chemotherapy and Opdivo plus Yervoy, as well as expanded efficacy and safety data from CheckMate -649, with both trials supporting Opdivo’s demonstrated superior first-line efficacy for patients with upper gastrointestinal cancers with high unmet needs. The CheckMate -648 data are part of the official ASCO press program on May 28, 2021.
• Expanded efficacy and safety results from CheckMate -577, the first and only trial to demonstrate superior efficacy of Opdivo monotherapy in the adjuvant setting in patients with esophageal or gastroesophageal junction cancer.
• Two- and four-year data from the CheckMate -9LA and CheckMate -227 trials, reinforcing the role of Opdivo plus Yervoy-based combinations in improving long-term survival for patients with non-small cell lung cancer (NSCLC) in the first-line setting.
• Surgical outcomes data from the CheckMate -816 trial that show the potential of neoadjuvant treatment with Opdivo plus chemotherapy to increase pathological response without negatively impacting surgery for patients with earlier-stage NSCLC.

Hematology

• Longer-term efficacy and safety results presented in collaboration with bluebird bio from the pivotal KarMMa study of Abecma (idecabtagene vicleucel), the first BCMA-directed CAR T cell therapy, in patients with relapsed or refractory multiple myeloma, reinforcing the company’s commitment to advancing cell therapies.
• First data disclosure from Phase 2 BEYOND study of Reblozyl (luspatercept), a first-in-class erythroid maturation agent, plus best supportive care, demonstrating its clinical benefit and potential in patients with non-transfusion-dependent beta (β)-thalassemia. These data are part of the official EHA press briefing and presidential symposium on June 11, 2021.
• New combination data from the Phase 1/2 MM-001 study of iberdomide, highlighting the potential of CELMoD^® compounds in patients with relapsed and refractory multiple myeloma and underscoring the company’s foundation in protein degradation research.
• Overall survival and progression-free survival analyses for Inrebic (fedratinib), the first treatment approved in Europe for myelofibrosis in nearly a decade, from the JAKARTA and JAKARTA-2 studies in patients with newly diagnosed and previously treated myelofibrosis.
• New analyses from QUAZAR AML-001 confirming survival benefits of Onureg (azacitidine tablets; CC-486) across different disease subtypes and baseline characteristics in patients with acute myeloid leukemia in the maintenance treatment setting.

Summary of Presentations

Select Bristol Myers Squibb studies at the 2021 ASCO Virtual Annual Meeting include:

Abstract Title	Author	Presentation Type/#	Session Title	Session Date/Time
Acute Myeloid Leukemia
Prognostic factors of overall (OS) and relapse-free survival (RFS) for patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy (IC): Multivariate analyses from the QUAZAR AML-001 trial of oral azacytidine (Oral-AZA)	Gail J. Roboz	Poster Discussion Abstract # 7014	Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant	Friday, June 4, 2021: 9:00 AM EDT
Gastrointestinal
Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): First results of the CheckMate 648 study	Ian Chau	Oral Abstract # LBA4001	Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary	Saturday, June 5, 2021: 1:45 PM - 4:45 PM EDT   ASCO Press Program Friday, May 28, 11:30 AM – 1:00 PM EDT
First-line (1L) nivolumab (NIVO) plus chemotherapy (chemo) versus chemo in advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): Expanded efficacy and safety data from CheckMate 649	Markus H. Moehler	Oral Abstract # 4002	Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary	Saturday, June 5, 2021: 1:45 PM - 4:45 PM EDT
Adjuvant nivolumab (NIVO) in resected esophageal or gastroesophageal junction cancer (EC/GEJC) following neoadjuvant chemoradiotherapy (CRT): Expanded efficacy and safety analyses from CheckMate 577	Ronan J. Kelly	Oral Abstract # 4003	Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary	Saturday, June 5, 2021: 1:45 PM - 4:45 PM EDT
Health-related quality of life (HRQOL) in patients (pts) with advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC) or esophageal adenocarcinoma (EAC): Interim results of nivolumab plus chemotherapy (N+C) versus (C) from CheckMate 649	Lucjan Wyrwicz	Poster Abstract # 4066	Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary	Friday, June 4, 2021: 9:00 AM EDT
Genitourinary
Nivolumab plus cabozantinib (N+C) versus sunitinib (S) for advanced renal cell carcinoma (aRCC): Outcomes by baseline disease characteristics in the phase 3 CheckMate 9ER trial	Andrea B. Apolo	Poster Abstract # 4553	Genitourinary Cancer—Kidney and Bladder	Friday, June 4, 2021: 9:00 AM EDT
Quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) of nivolumab plus cabozantinib (N+C) versus sunitinib (SUN) in treatment-naïve, advanced/metastatic renal cell carcinoma (aRCC): A post-hoc analysis of CheckMate 9ER (CM 9ER) data	David Cella	Poster Abstract # 6567	Health Services Research and Quality Improvement	Friday, June 4, 2021: 9:00 AM EDT
Long-term trend of quality-adjusted time without symptoms or toxicities (Q-TWiST) of nivolumab+ipilimumab (N+I) versus sunitinib (SUN) for the first-line treatment of advanced renal cell carcinoma (aRCC)	Robert J. Motzer	Poster Abstract # 6568	Health Services Research and Quality Improvement	Friday, June 4, 2021: 9:00 AM EDT
Efficacy outcomes of nivolumab + cabozantinib versus pembrolizumab + axitinib in patients with advanced renal cell carcinoma (aRCC): Matching-adjusted indirect comparison (MAIC)​	Bradley A. McGregor	Poster Abstract # 4578	Genitourinary Cancer—Kidney and Bladder	Friday, June 4, 2021: 9:00 AM EDT
Impact of recurrence on health-related quality of life in patients at high risk of recurrence after radical surgery for muscle-invasive urothelial carcinoma (MIUC): Results from the phase 3 CheckMate 274 trial	Matthew D. Galsky	Poster Abstract # 4540	Genitourinary Cancer—Kidney and Bladder	Friday, June 4, 2021: 9:00 AM EDT
Safety and efficacy outcomes with nivolumab plus ipilimumab in patients with advanced renal cell carcinoma and brain metastases: results from the CheckMate 920 trial	Hamid Emamekhoo	Poster Discussion Abstract # 4515	Genitourinary Cancer—Kidney and Bladder	Friday, June 4, 2021: 9:00 AM EDT
Melanoma
Relatlimab (RELA) plus nivolumab (NIVO) versus NIVO in first-line advanced melanoma: Primary phase III results from RELATIVITY-047 (CA224-047)	Evan J. Lipson	Oral Abstract # 9503	Melanoma/Skin Cancers	Sunday, June 6, 2021: 8:00 AM-11:00 AM EDT   ASCO Press Program Friday, May 14, 10:45 AM – 12:00 PM EDT
CheckMate 067: 6.5-year outcomes in patients (pts) with advanced melanoma	Jedd D. Wolchok	Oral Abstract # 9506	Melanoma/Skin Cancers	Sunday, June 6, 2021: 8:00 AM-11:00 AM EDT
Two dosing regimens of nivolumab (NIVO) plus ipilimumab (IPI) for advanced (adv) melanoma: Three-year results of CheckMate 511	Celeste Lebbé	Poster Discussion Abstract # 9516	Melanoma/Skin Cancers	Friday, June 4, 2021: 9:00 AM EDT
Analysis of patients (pts) with in-transit metastases treated with nivolumab (NIVO) or ipilimumab (IPI) in CheckMate 238	James Larkin	Poster Abstract # 9569	Melanoma/Skin Cancers	Friday, June 4, 2021: 9:00 AM EDT
Treatment outcomes in patients (pts) with melanoma brain metastases (MBM) treated with systemic therapy: A systematic literature review (SLR) and meta-analysis	Hussein A. Tawbi	Poster Abstract # 9561	Melanoma/Skin Cancers	Friday, June 4, 2021: 9:00 AM EDT
Association of health-related quality of life (HRQoL) and treatment safety with nivolumab (NIVO) in patients (pts) with resected stage IIIB/C or IV melanoma: Analysis of CheckMate 238 four-year follow-up (FU) data	Jeffery S. Weber	Poster Abstract # 9574	Melanoma/Skin Cancers	Friday, June 4, 2021: 9:00 AM EDT
Multiple Myeloma
Characteristics of neurotoxicity associated with idecabtagene vicleucel (ide-cel, bb2121) in patients with relapsed and refractory multiple myeloma (RRMM) in the pivotal phase II KarMMa study	Salomon Manier	Poster Abstract # 8036	Hematologic Malignancies—Plasma Cell Dyscrasia	Friday, June 4, 2021: 9:00 AM EDT
Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in relapsed and refractory multiple myeloma: Updated KarMMa results	Larry D. Anderson, Jr	Poster Discussion Abstract # 8016	Hematologic Malignancies—Plasma Cell Dyscrasia	Friday, June 4, 2021: 9:00 AM EDT
KarMMa-4: Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy in high-risk newly diagnosed multiple myeloma	Saad Z. Usmani	Poster Abstract # TPS8053	Hematologic Malignancies—Plasma Cell Dyscrasia	Friday, June 4, 2021: 9:00 AM EDT
Product Design & Delivery
CheckMate 8KX: Phase 1/2 multitumor preliminary analyses of a subcutaneous formulation of nivolumab (± rHuPH20)	Sara Lonardi	Poster Abstract # 2575	Developmental Therapeutics – Immunotherapy	Friday, June 4, 2021: 9:00 AM EDT
Thoracic
Nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for advanced non-small cell lung cancer (NSCLC): 4-year update from CheckMate 227	Luis G. Paz-Ares	Poster Discussion Abstract # 9016	Lung Cancer—Non-Small Cell Metastatic	Friday, June 4, 2021: 9:00 AM EDT
First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA	Martin Reck	Oral Abstract # 9000	Lung Cancer—Non-Small Cell Metastatic	Friday, June 4, 2021: 1:00 PM - 4:00 PM EDT
Surgical outcomes from the phase 3 CheckMate 816 trial: Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo alone as neoadjuvant treatment for patients with resectable non-small cell lung cancer (NSCLC)	Jonathan Spicer	Oral Abstract # 8503	Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers	Sunday, June 6, 2021: 8:00 AM – 11:00 AM EDT

Select Bristol Myers Squibb studies at the 2021 EHA Virtual Congress include:

Abstract Title	Author	Presentation Type/#
Acute Myeloid Leukemia
Survival Outcomes From the QUAZAR AML-001 Trial With Oral Azacitidine for Patients With Acute Myeloid Leukemia in Remission by Disease Subtype, Cytogenetic Risk, and NPM1 Mutation Status at Diagnosis	Hartmut Döhner	Oral Abstract # S131
Estimated Hospitalization-Related Costs With Oral-AZA vs PBO for Remission Maintenance in Patients With AML in Spain and the UK	Christopher Pocock	Oral Abstract # S311
Patient Preferences for Maintenance Therapy of Acute Myeloid Leukemia: A Discrete Choice Experiment Subanalysis of Patients in Germany and Italy	Katelyn Cutts	Publication # PB1398
A Phase 3 Study of Enasidenib Versus Conventional Care Regimens in Older Patients With Late-Stage Mutant-IDH2 R/R AML	Courtney DiNardo	Poster Abstract # EP457
Updated Pharmacodynamic and Survival Outcomes From the AG221-AML-005 Trial of Enasidenib Plus AZA in Patients With Newly Diagnosed Mutant IDH2 AML	Courtney DiNardo	Poster Abstract # EP465
Beta Thalassemia
The BEYOND Study: Results of a Phase 2, Double-blind, Randomized, Placebo (Pbo)-Controlled Multicenter Study of Luspatercept in Adult Patients (Pts) With Non-transfusion Dependent (Ntd) β-Thalassemia	Ali Taher	Oral Presidential Symposium # S101
Benefit of Continuing Therapy With Luspatercept in Patients With Beta-Thalassemia Who Do Not Achieve ≥33% Reduction in Red Blood Cell (RBC) Transfusion Burden (TB) in Weeks 13-24 in the BELIEVE Trial	Antonio Piga	Poster Abstract # EP1306
Fewer Red Blood Cell Transfusion Units and Visits Across Baseline Transfusion Burden Levels in Patients With Beta-Thalassemia Treated With Luspatercept in the Phase 3 BELIEVE Trial	Ali Taher	Poster Abstract # EP1304
Lymphoma
Safety & Efficacy Preliminary Results From a Phase 2 Study of Lisocabtagene Maraleucel (liso-cel) in the Non-university Setting	JT Godwin	Poster Abstract # EP541
Clinical Outcomes in Patients With Relapsed/Refractory Large B-Cell Lymphoma Receiving Third-Line Therapy: A Multicenter, Retrospective, Real-world Study in the United Kingdom	Christopher Fox	Poster Abstract # EP539
Multiple Myeloma
Characteristics of Neurotoxicity Associated With Idecabtagene Vicleucel (Ide-cel, bb2121) in Patients With Relapsed and Refractory Multiple Myeloma in the Pivotal Phase 2 KarMMa Study	Salomon Manier	Poster Abstract # EP984
Idecabtagene Vicleucel (Ide-cel, bb2121), a BCMA-Directed CAR T Cell Therapy, in Patients With Relapsed and Refractory Multiple Myeloma: Updated KarMMa Results	Albert Oriol	Poster Abstract # EP1009
Iberdomide (Iber) in Combination With Dexamethasone (Dex) and Daratumumab (Dara), Bortezomib (Bort), or Carfilzomib (Cfz) in Patients (Pts) With Relapsed/Refractory Multiple Myeloma (RRMM)	Sagar Lonial	Oral Abstract # S187
Pharmacokinetic/Pharmacodynamic Evaluation of Iberdomide (Iber) in Combination With Dexamethasone and Daratumumab in a Phase 1/2 Trial for Relapsed/Refractory Multiple Myeloma	Michael Amatangelo	Publication # PB1632
Myelodysplastic Syndrome
Benefit of Continuing Luspatercept Therapy in Patients With Lower-risk Myelodysplastic Syndromes Who Did Not Achieve Red Blood Cell Transfusion Independence by Week 25 in the MEDALIST Study	Ulrich Germing	Poster Abstract # EP915
Luspatercept Reduces Red Blood Cell Transfusions in Patients With Lower-Risk Myelodysplastic Syndromes Regardless of Baseline Transfusion Burden in the MEDALIST Study	Guillermo Garcia-Manero	Poster Abstract # EP920
Health-Related Quality of Life (HRQoL) in Patients (Pts) With Myelodysplastic Syndromes (MDS) in the CONNECT® Myeloid Disease Registry	Dennis Revicki	Poster Abstract # EP1182
Myelofibrosis
Overall and Progression-free Survival in Patients Treated With Fedratinib as First-line MF Therapy and After Prior RUX: Results From the JAKARTA and JAKARTA2 Trials	Claire Harrison	Oral Abstract # S203

The abstracts above are available on the EHA conference website. All presentations will be available on demand when published on the virtual congress platform on Friday, June 11, at 9:00 AM CEST (3 AM EDT).

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

OPDIVO Indications

OPDIVO^® (nivolumab), as a single agent, is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

OPDIVO^® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab), is indicated for the first-line treatment of patients with intermediate or poor risk advanced renal cell carcinoma (RCC).

OPDIVO^® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

OPDIVO^® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO^® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO^® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO^® (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO^® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO^® (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab), is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO^® (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

OPDIVO^® (nivolumab) is indicated for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

OPDIVO^® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO or YERVOY interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

Immune-Mediated Pneumonitis

OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.9%), and Grade 2 (2.1%). In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 10% (5/49) of patients. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 3.9% (26/666) of patients, including Grade 3 (1.4%) and Grade 2 (2.6%). In NSCLC patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, immune-mediated pneumonitis occurred in 9% (50/576) of patients, including Grade 4 (0.5%), Grade 3 (3.5%), and Grade 2 (4.0%). Four patients (0.7%) died due to pneumonitis.

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 6.0% (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients receiving OPDIVO, including Grade 3 (n=1) and Grade 2 (n=12).

Immune-Mediated Colitis

OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients, including Grade 3 (1.7%) and Grade 2 (1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25% (115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and Grade 2 (8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated colitis occurred in 9% (60/666) of patients, including Grade 3 (4.4%) and Grade 2 (3.7%).

In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, immune-mediated colitis occurred in 12% (62/511) of patients, including Grade 3-5 (7%) and Grade 2 (5%).

Immune-Mediated Hepatitis and Hepatotoxicity

OPDIVO and YERVOY can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%), Grade 3 (1.3%), and Grade 2 (0.4%). In patients receiving OPDIVO monotherapy in Checkmate 040, immune-mediated hepatitis requiring systemic corticosteroids occurred in 5% (8/154) of patients. In patients receiving OPDIVO 1 mg/ kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 15% (70/456) of patients, including Grade 4 (2.4%), Grade 3 (11%), and Grade 2 (1.8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 7% (48/666) of patients, including Grade 4 (1.2%), Grade 3 (4.9%), and Grade 2 (0.4%).

In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, immune-mediated hepatitis occurred in 4.1% (21/511) of patients, including Grade 3-5 (1.6%) and Grade 2 (2.5%).

OPDIVO in combination with cabozantinib can cause hepatic toxicity with higher frequencies of Grade 3 and 4 ALT and AST elevations compared to OPDIVO alone. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. In patients receiving OPDIVO and cabozantinib, Grades 3 and 4 increased ALT or AST were seen in 11% of patients.

Immune-Mediated Endocrinopathies

OPDIVO and YERVOY can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated.

In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994), including Grade 3 (0.4%) and Grade 2 (0.6%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, adrenal insufficiency occurred in 8% (35/456), including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, adrenal insufficiency occurred in 7% (48/666) of patients, including Grade 4 (0.3%), Grade 3 (2.5%), and Grade 2 (4.1%). In patients receiving OPDIVO and cabozantinib, adrenal insufficiency occurred in 4.7% (15/320) of patients, including Grade 3 (2.2%) and Grade 2 (1.9%).

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypophysitis occurred in 9% (42/456), including Grade 3 (2.4%) and Grade 2 (6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypophysitis occurred in 4.4% (29/666) of patients, including Grade 4 (0.3%), Grade 3 (2.4%), and Grade 2 (0.9%).

In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, thyroiditis occurred in 2.7% (22/666) of patients, including Grade 3 (4.5%) and Grade 2 (2.2%).

In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (<0.1%) and Grade 2 (1.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hyperthyroidism occurred in 9% (42/456) of patients, including Grade 3 (0.9%) and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hyperthyroidism occurred in 12% (80/666) of patients, including Grade 3 (0.6%) and Grade 2 (4.5%).

In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of patients, including Grade 3 (0.4%) and Grade 2 (11%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypothyroidism occurred in 18% (122/666) of patients, including Grade 3 (0.6%) and Grade 2 (11%).

In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2 (0.3%), and 2 cases of diabetic ketoacidosis. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, diabetes occurred in 2.7% (15/666) of patients, including Grade 4 (0.6%), Grade 3 (0.3%), and Grade 2 (0.9%).

In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, Grade 2-5 immune-mediated endocrinopathies occurred in 4% (21/511) of patients. Severe to life-threatening (Grade 3-4) endocrinopathies occurred in 9 (1.8%) patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. Six of the 9 patients were hospitalized for severe endocrinopathies. Moderate (Grade 2) endocrinopathy occurred in 12 patients (2.3%), including hypothyroidism, adrenal insufficiency, hypopituitarism, hyperthyroidism and Cushing’s syndrome.

Immune-Mediated Nephritis with Renal Dysfunction

OPDIVO and YERVOY can cause immune-mediated nephritis. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.5%), and Grade 2 (0.6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated nephritis with renal dysfunction occurred in 4.1% (27/666) of patients, including Grade 4 (0.6%), Grade 3 (1.1%), and Grade 2 (2.2%).

Immune-Mediated Dermatologic Adverse Reactions

OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes.

YERVOY can cause immune-mediated rash or dermatitis, including bullous and exfoliative dermatitis, SJS, TEN, and DRESS. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/ exfoliative rashes.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients, including Grade 3 (1.1%) and Grade 2 (2.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated rash occurred in 28% (127/456) of patients, including Grade 3 (4.8%) and Grade 2 (10%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated rash occurred in 16% (108/666) of patients, including Grade 3 (3.5%) and Grade 2 (4.2%).

In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, immune-mediated rash occurred in 15% (76/511) of patients, including Grade 3-5 (2.5%) and Grade 2 (12%).

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received OPDIVO monotherapy or OPDIVO in combination with YERVOY or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions: cardiac/vascular: myocarditis, pericarditis, vasculitis; nervous system: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; ocular: uveitis, iritis, and other ocular inflammatory toxicities can occur; gastrointestinal: pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis; musculoskeletal and connective tissue: myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica; endocrine: hypoparathyroidism; other (hematologic/immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

In addition to the immune-mediated adverse reactions listed above, across clinical trials of YERVOY monotherapy or in combination with OPDIVO, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1% of patients unless otherwise specified: nervous system: autoimmune neuropathy (2%), myasthenic syndrome/myasthenia gravis, motor dysfunction; cardiovascular: angiopathy, temporal arteritis; ocular: blepharitis, episcleritis, orbital myositis, scleritis; gastrointestinal: pancreatitis (1.3%); other (hematologic/immune): conjunctivitis, cytopenias (2.5%), eosinophilia (2.1%), erythema multiforme, hypersensitivity vasculitis, neurosensory hypoacusis, psoriasis.

Some ocular IMAR cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, which has been observed in patients receiving OPDIVO and YERVOY, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.

Infusion-Related Reactions

OPDIVO and YERVOY can cause severe infusion-related reactions. Discontinue OPDIVO and YERVOY in patients with severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild (Grade 1) or moderate (Grade 2) infusion-related reactions. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate trial in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO. In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 8% (4/49) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, infusion-related reactions occurred in 5.1% (28/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, infusion-related reactions occurred in 4.2% (5/119) of patients. In MPM patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, infusion-related reactions occurred in 12% (37/300) of patients.

In separate Phase 3 trials of YERVOY 3 mg/kg and 10 mg/kg monotherapy, infusion-related reactions occurred in 2.9% (28/982) of patients.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with OPDIVO or YERVOY. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between OPDIVO or YERVOY and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with OPDIVO and YERVOY prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal studies, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. The effects of YERVOY are likely to be greater during the second and third trimesters of pregnancy. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and YERVOY and for at least 5 months after the last dose.

Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a Thalidomide Analogue and Dexamethasone

In randomized clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

Lactation

There are no data on the presence of OPDIVO or YERVOY in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 5 months after the last dose.

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (74% and 44%), adverse reactions leading to permanent discontinuation (47% and 18%) or to dosing delays (58% and 36%), and Grade 3 or 4 adverse reactions (72% and 51%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.2%), colitis (10% and 1.9%), and pyrexia (10% and 1.0%). In Checkmate 227, serious adverse reactions occurred in 58% of patients (n=576). The most frequent (≥2%) serious adverse reactions were pneumonia, diarrhea/colitis, pneumonitis, hepatitis, pulmonary embolism, adrenal insufficiency, and hypophysitis. Fatal adverse reactions occurred in 1.7% of patients; these included events of pneumonitis (4 patients), myocarditis, acute kidney injury, shock, hyperglycemia, multi-system organ failure, and renal failure. In Checkmate 9LA, serious adverse reactions occurred in 57% of patients (n=358). The most frequent (>2%) serious adverse reactions were pneumonia, diarrhea, febrile neutropenia, anemia, acute kidney injury, musculoskeletal pain, dyspnea, pneumonitis, and respiratory failure. Fatal adverse reactions occurred in 7 (2%) patients, and included hepatic toxicity, acute renal failure, sepsis, pneumonitis, diarrhea with hypokalemia, and massive hemoptysis in the setting of thrombocytopenia. In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 057, fatal adverse reactions occurred; these included events of infection (7 patients, including one case of Pneumocystis jirovecii pneumonia), pulmonary embolism (4 patients), and limbic encephalitis (1 patient). In Checkmate 743, serious adverse reactions occurred in 54% of patients receiving OPDIVO plus YERVOY. The most frequent serious adverse reactions reported in ≥2% of patients were pneumonia, pyrexia, diarrhea, pneumonitis, pleural effusion, dyspnea, acute kidney injury, infusion-related reaction, musculoskeletal pain, and pulmonary embolism. Fatal adverse reactions occurred in 4 (1.3%) patients and included pneumonitis, acute heart failure, sepsis, and encephalitis. In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving OPDIVO plus YERVOY (n=547). The most frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea, adrenal insufficiency, and colitis. In Checkmate 9ER, serious adverse reactions occurred in 48% of patients receiving OPDIVO and cabozantinib (n=320). The most frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pneumonia, pneumonitis, pulmonary embolism, urinary tract infection, and hyponatremia. Fatal intestinal perforations occurred in 3 (0.9%) patients. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, adverse reactions leading to discontinuation occurred in 7% and dose delays due to adverse reactions occurred in 34% of patients (n=266). Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions reported in ≥1% of patients were pneumonia, infusion-related reaction, pyrexia, colitis or diarrhea, pleural effusion, pneumonitis, and rash. Eleven patients died from causes other than disease progression: 3 from adverse reactions within 30 days of the last OPDIVO dose, 2 from infection 8 to 9 months after completing OPDIVO, and 6 from complications of allogeneic HSCT. In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO (n=236). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration. In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO with YERVOY (n=119), serious adverse reactions occurred in 47% of patients. The most frequent serious adverse reactions reported in ≥2% of patients were colitis/diarrhea, hepatic events, abdominal pain, acute kidney injury, pyrexia, and dehydration. In Checkmate 040, serious adverse reactions occurred in 49% of patients receiving OPDIVO (n=154). The most frequent serious adverse reactions reported in ≥2% of patients were pyrexia, ascites, back pain, general physical health deterioration, abdominal pain, pneumonia, and anemia. In Checkmate 040, serious adverse reactions occurred in 59% of patients receiving OPDIVO with YERVOY (n=49). Serious adverse reactions reported in ≥4% of patients were pyrexia, diarrhea, anemia, increased AST, adrenal insufficiency, ascites, esophageal varices hemorrhage, hyponatremia, increased blood bilirubin, and pneumonitis. In Checkmate 238, serious adverse reactions occurred in 18% of patients receiving OPDIVO (n=452). Grade 3 or 4 adverse reactions occurred in 25% of OPDIVO-treated patients (n=452). The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of OPDIVO-treated patients were diarrhea and increased lipase and amylase. In Attraction-3, serious adverse reactions occurred in 38% of patients receiving OPDIVO (n=209). Serious adverse reactions reported in ≥2% of patients who received OPDIVO were pneumonia, esophageal fistula, interstitial lung disease, and pyrexia. The following fatal adverse reactions occurred in patients who received OPDIVO: interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%). In Checkmate 649, serious adverse reactions occurred in 52% of patients treated with OPDIVO in combination with chemotherapy (n=782). The most frequent serious adverse reactions reported in ≥ 2% of patients treated with OPDIVO in combination with chemotherapy were vomiting (3.7%), pneumonia (3.6%), anemia (3.6%), pyrexia (2.8%), diarrhea (2.7%), febrile neutropenia (2.6%), and pneumonitis (2.4%). Fatal adverse reactions occurred in 16 (2.0%) patients who were treated with OPDIVO in combination with chemotherapy; these included pneumonitis (4 patients), febrile neutropenia (2 patients), stroke (2 patients), gastrointestinal toxicity, intestinal mucositis, septic shock, pneumonia, infection, gastrointestinal bleeding, mesenteric vessel thrombosis, and disseminated intravascular coagulation.

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (62%), diarrhea (54%), rash (53%), nausea (44%), pyrexia (40%), pruritus (39%), musculoskeletal pain (32%), vomiting (31%), decreased appetite (29%), cough (27%), headache (26%), dyspnea (24%), upper respiratory tract infection (23%), arthralgia (21%), and increased transaminases (25%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO arm (n=313) were fatigue (59%), rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea (30%), cough (28%), pruritus (27%), upper respiratory tract infection (22%), decreased appetite (22%), headache (22%), constipation (21%), arthralgia (21%), and vomiting (20%). In Checkmate 227, the most common (≥20%) adverse reactions were fatigue (44%), rash (34%), decreased appetite (31%), musculoskeletal pain (27%), diarrhea/colitis (26%), dyspnea (26%), cough (23%), hepatitis (21%), nausea (21%), and pruritus (21%). In Checkmate 9LA, the most common (>20%) adverse reactions were fatigue (49%), musculoskeletal pain (39%), nausea (32%), diarrhea (31%), rash (30%), decreased appetite (28%), constipation (21%), and pruritus (21%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 743, the most common adverse reactions (≥20%) in patients receiving OPDIVO plus YERVOY were fatigue (43%), musculoskeletal pain (38%), rash (34%), diarrhea (32%), dyspnea (27%), nausea (24%), decreased appetite (24%), cough (23%), and pruritus (21%). In Checkmate 214, the most common adverse reactions (≥20%) reported in patients treated with OPDIVO plus YERVOY (n=547) were fatigue (58%), rash (39%), diarrhea (38%), musculoskeletal pain (37%), pruritus (33%), nausea (30%), cough (28%), pyrexia (25%), arthralgia (23%), decreased appetite (21%), dyspnea (20%), and vomiting (20%). In Checkmate 9ER, the most common adverse reactions (≥20%) in patients receiving OPDIVO and cabozantinib (n=320) were diarrhea (64%), fatigue (51%), hepatotoxicity (44%), palmar-plantar erythrodysaesthesia syndrome (40%), stomatitis (37%), rash (36%), hypertension (36%), hypothyroidism (34%), musculoskeletal pain (33%), decreased appetite (28%), nausea (27%), dysgeusia (24%), abdominal pain (22%), cough (20%) and upper respiratory tract infection (20%). In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were fatigue (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=266) were upper respiratory tract infection (44%), fatigue (39%), cough (36%), diarrhea (33%), pyrexia (29%), musculoskeletal pain (26%), rash (24%), nausea (20%) and pruritus (20%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO (n=236) were cough (14%) and dyspnea (14%) at a higher incidence than investigator’s choice. In Checkmate 275, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%). In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO as a single agent (n=74), the most common adverse reactions (≥20%) were fatigue (54%), diarrhea (43%), abdominal pain (34%), nausea (34%), vomiting (28%), musculoskeletal pain (28%), cough (26%), pyrexia (24%), rash (23%), constipation (20%), and upper respiratory tract infection (20%). In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO with YERVOY (n=119), the most common adverse reactions (≥20%) were fatigue (49%), diarrhea (45%), pyrexia (36%), musculoskeletal pain (36%), abdominal pain (30%), pruritus (28%), nausea (26%), rash (25%), decreased appetite (20%), and vomiting (20%). In Checkmate 040, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=154) were fatigue (38%), musculoskeletal pain (36%), abdominal pain (34%), pruritus (27%), diarrhea (27%), rash (26%), cough (23%), and decreased appetite (22%). In Checkmate 040, the most common adverse reactions (≥20%) in patients receiving OPDIVO with YERVOY (n=49), were rash (53%), pruritus (53%), musculoskeletal pain (41%), diarrhea (39%), cough (37%), decreased appetite (35%), fatigue (27%), pyrexia (27%), abdominal pain (22%), headache (22%), nausea (20%), dizziness (20%), hypothyroidism (20%), and weight decreased (20%). In Checkmate 238, the most common adverse reactions (≥20%) reported in OPDIVO-treated patients (n=452) vs ipilimumab-treated patients (n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22% vs 15%), and abdominal pain (21% vs 23%). The most common immune-mediated adverse reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%). In Attraction-3, the most common adverse reactions (≥20%) in OPDIVO-treated patients (n=209) were rash (22%) and decreased appetite (21%). In Checkmate 649, the most common adverse reactions (≥20%) in patients treated with OPDIVO in combination with chemotherapy (n=782) were peripheral neuropathy (53%), nausea (48%), fatigue (44%), diarrhea (39%), vomiting (31%), decreased appetite (29%), abdominal pain (27%), constipation (25%), and musculoskeletal pain (20%).

In a separate Phase 3 trial of YERVOY 3 mg/kg, the most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).

Please see US Full Prescribing Information for OPDIVO and YERVOY.

Clinical Trials and Patient Populations

Checkmate 037–previously treated metastatic melanoma; Checkmate 066–previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 227–previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 025–previously treated renal cell carcinoma; Checkmate 205/039–classical Hodgkin lymphoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 275–urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 040–hepatocellular carcinoma, as a single agent or in combination with YERVOY; Checkmate 238–adjuvant treatment of melanoma; Attraction-3–esophageal squamous cell carcinoma; Checkmate 649–previously untreated advanced or metastatic gastric or gastroesophageal junction or esophageal adenocarcinoma.

ABECMA Indication

ABECMA (idecab