On December 8, 2025 Bristol Myers Squibb (NYSE: BMY) reported its hematology leadership through new research across multiple therapies for patients with lymphoma at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.
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Highlights include updates from the company’s targeted protein degradation pipeline, including data on first-in-class investigational lymphoma CELMoD agent golcadomide and first-in-class BCL6 ligand-directed degrader BMS-986458; alongside long-term results for Breyanzi (lisocabtagene maraleucel; liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, from the Phase 3 TRANSFORM and Phase 2 TRANSCEND FL trials.
"The data presented at ASH (Free ASH Whitepaper) represent a significant step forward in our pursuit of transformative outcomes for patients with lymphoma, who urgently need more effective and durable treatment options," said Anne Kerber, senior vice president, head of development, Hematology, Oncology and Cell Therapy, Bristol Myers Squibb. "From the potential of golcadomide to offer meaningful benefit in aggressive B-cell and follicular lymphomas, to the innovative mechanism of our BCL6 ligand-directed degrader, BMS-986458, and the proven, long-term efficacy of Breyanzi – these collective results underscore our dedication to pioneering therapies that make a real difference for patients."
Targeted Protein Degradation
Two-year follow-up of golcadomide plus R-CHOP in patients with previously untreated aggressive B-cell lymphoma (Abstract #476): At median follow-up of 24 months, golcadomide 0.4 mg plus R-CHOP continued to demonstrate deep, durable responses and promising progression-free survival (PFS).
PFS rate of 79% across overall and high-risk populations.
Complete metabolic response rate (CMR) was 88% and minimal residual disease (MRD) negativity rate was 90%, irrespective of cell of origin.
In high-risk patients, CMR was 89% and MRD negativity was 93%.
Predictable and manageable safety was observed with no new safety signals observed.
Data support the ongoing Phase 3 GOLSEEK-1 study in this high-risk population.
Extended follow-up of golcadomide plus rituximab in patients with relapsed or refractory follicular lymphoma (Abstract #1006) and relapsed or refractory diffuse large B-cell lymphoma (Abstract #479): Golcadomide plus rituximab continued to show promising efficacy and durable responses in heavily pre-treated patients with relapsed or refractory follicular lymphoma (R/R FL) and relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), including in those with prior T-cell redirecting therapy.
In FL, golcadomide 0.4 mg plus rituximab showed an overall response rate (ORR) of 97% and a complete response rate (CRR) of 78%.
In DLBCL, golcadomide 0.4 mg plus rituximab showed an ORR of 58% and a CRR of 44%.
No new safety signals in either patient population were observed.
Data support the ongoing Phase 3 GOLSEEK-4 study in FL who have received at least one prior line of systemic therapy.
Updated results from dose-escalation study of BMS-986458 monotherapy in heavily pre-treated relapsed or refractory non-Hodgkin lymphoma (Abstract #480): BMS-986458, an investigational ligand-directed-degrader targeting BCL6, continued to show promising preliminary efficacy and acceptable tolerability in patients with heavily pre-treated R/R DLBCL and FL, with mainly low-grade adverse events.
Strong antitumor activity was confirmed, with an ORR of 65% (54% in DLBCL and 80% in FL) and a CRR of 21% (7% in DLBCL and 40% in FL).
Data support continued development of BMS-986458 as a monotherapy or combination therapy for non-Hodgkin lymphoma (NHL).
"The updated data for our BCL6-targeting ligand-directed degrader reinforce the promise of ligand-directed degradation as a novel approach for patients with relapsed or refractory non-Hodgkin lymphoma," said Michael Pourdehnad, senior vice president, head of early clinical development, Hematology, Oncology and Cell Therapy, Bristol Myers Squibb. "Seeing strong antitumor activity and meaningful responses, even in heavily pre-treated populations, underscores the potential of this mechanism to address critical unmet needs and advance the standard of care."
Cell Therapy
Long-term follow-up results of patients treated with Breyanzi in TRANSFORM study (Abstract #3710): In a four-year follow-up, combining data from TRANSFORM and long-term follow-up (LTFU) studies, Breyanzi continued to demonstrate long-term clinical benefit with high PFS and overall survival (OS) rates in patients with second-line relapsed or refractory large B-cell lymphoma (LBCL). Upon completion of TRANSFORM, patients treated with Breyanzi could choose to enroll in a separate LTFU study.
Median PFS (95% CI: 12.6–NR) and OS (95% CI: NR–NR) were not reached (NR).
The four-year landmark PFS and OS rates were 52.2% (95% CI: 41.5–62.8) and 61.5% (95% CI: 51.2–71.7), respectively.
Breyanzi continued to demonstrate a consistent safety profile with no new safety signals observed compared with previous results from TRANSFORM.
Three-year follow-up with Breyanzi in the TRANSCEND FL study (Abstract #467): Three-year follow-up results from TRANSCEND FL showed that a single infusion of Breyanzi continued to demonstrate high rates of deep and durable responses.
Complete response (CR) rate was 94% with 70% of patients still in response at 36-months (duration of response [DOR]).
36-month OS was 86% and PFS was 68% in patients with third-line or later R/R FL.
Consistently high efficacy was seen across subgroups with ORR of 96%-100% and three-year ongoing response rates of 60%-83%, including in patients with high-risk characteristics (progression of disease within 24 months (POD24), bulky disease, double-refractory disease).
Safety was consistent with the primary and two-year follow-up analyses.
"Results from the TRANSFORM and TRANSCEND FL trials are a remarkable display of the treatment Breyanzi can provide for patients living with certain B-cell lymphomas, offering improved outcomes and consistent safety profile," said Lynelle B. Hoch, president, Cell Therapy Organization, Bristol Myers Squibb. "These trial results are reinforced by what we’ve seen in the real world – cell therapy continues to revolutionize the treatment of certain types of blood cancer with deep and durable responses, further inspiring us at BMS to continue driving this modality forward for patients."
Bristol Myers Squibb thanks the patients and investigators involved in these clinical trials.
About Breyanzi
Breyanzi is a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells. Breyanzi is made from a patient’s own T cells, which are collected and genetically reengineered to become CAR T cells that are then delivered via infusion as a one-time treatment. The treatment process includes blood collection, CAR T cell creation, potential bridging therapy, lymphodepletion, administration, and side-effect monitoring.
Breyanzi is approved in the U.S. for the treatment of relapsed or refractory large B-cell lymphoma (LBCL) after at least one prior line of therapy, has received accelerated approval for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior lines of therapy, relapsed or refractory follicular lymphoma (FL) after two or more prior lines of systemic therapy, relapsed or refractory mantle cell lymphoma (MCL) after at least two prior lines of systemic therapy, and relapsed or refractory marginal zone lymphoma (MZL) after at least two prior lines of systemic therapy. Breyanzi is also approved in Japan, the European Union (EU), Switzerland, Israel, the United Kingdom (UK), and Canada for the treatment of relapsed or refractory LBCL after at least one prior line of therapy; in Japan for the treatment of patients with relapsed or refractory high-risk FL after one prior line of systemic therapy, and in patients with relapsed or refractory FL after two or more lines of systemic therapy; in the EU, Switzerland, Israel, and the UK for the treatment of relapsed or refractory FL after two or more lines of systemic therapy; and in the EU and Israel for the treatment of relapsed or refractory MCL after at least two lines of systemic therapy including a Bruton’s tyrosine kinase (BTK) inhibitor.
Breyanzi U.S. FDA-Approved Indications
BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:
adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:
refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or
relapsed or refractory disease after two or more lines of systemic therapy.
Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.
adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
adult patients with relapsed or refractory follicular lymphoma (FL) who have received 2 or more prior lines of systemic therapy. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor.
adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least 2 prior lines of systemic therapy.
Breyanzi U.S. Important Safety Information
WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, AND SECONDARY HEMATOLOGICAL MALIGNANCIES
Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving BREYANZI. Do not administer BREYANZI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving BREYANZI, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with BREYANZI. Provide supportive care and/or corticosteroids as needed.
T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI.
Cytokine Release Syndrome
Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. In clinical trials of BREYANZI, which enrolled a total of 769 patients with non-Hodgkin lymphoma (NHL), CRS occurred in 56% of patients, including ≥ Grade 3 CRS in 3.4% of patients. The median time to onset was 5 days (range: 1 to 63 days). CRS resolved in 99% of patients with a median duration of 5 days (range: 1 to 37 days). One patient had fatal CRS and 5 patients had ongoing CRS at the time of death. The most common manifestations of CRS (≥10%) were fever, hypotension, chills, tachycardia, hypoxia, and headache.
Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI.
Neurologic Toxicities
Neurologic toxicities that were fatal or life-threatening, including immune effector cell-associated neurotoxicity syndrome (ICANS), occurred following treatment with BREYANZI. Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, also occurred.
In clinical trials of BREYANZI, CAR T cell-associated neurologic toxicities occurred in 32% of patients, including ≥ Grade 3 cases in 10% of patients. The median time to onset of neurotoxicity was 8 days (range: 1 to 63 days). Neurologic toxicities resolved in 88% of patients with a median duration of 7.5 days (range: 1 to 119 days). Of patients developing neurotoxicity, 83% also developed CRS.
The most common neurologic toxicities (≥5%) included encephalopathy, tremor, aphasia, delirium, and headache.
CRS and Neurologic Toxicities Monitoring
Monitor patients daily for at least 7 days following BREYANZI infusion for signs and symptoms of CRS and neurologic toxicities and assess for other causes of neurological symptoms. Continue to monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 2 weeks after infusion and treat promptly. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. Manage neurologic toxicity with supportive care and/or corticosteroid as needed. Advise patients to avoid driving for at least 2 weeks following infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time.
Hypersensitivity Reactions
Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO).
Serious Infections
Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion. In clinical trials of BREYANZI, infections of any grade occurred in 33% of patients, with Grade 3 or higher infections occurring in 12% of all patients. Grade 3 or higher infections with an unspecified pathogen occurred in 7%, bacterial infections in 3.5%, viral infections in 2%, and fungal infections in 0.7% of patients. One patient who received 4 prior lines of therapy developed a fatal case of John Cunningham (JC) virus progressive multifocal leukoencephalopathy 4 months after treatment with BREYANZI. One patient who received 3 prior lines of therapy developed a fatal case of cryptococcal meningoencephalitis 35 days after treatment with BREYANZI.
Febrile neutropenia developed after BREYANZI infusion in 8% of patients. Febrile neutropenia 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.
Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines. Avoid administration of BREYANZI in patients with clinically significant, active systemic infections.
Viral reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. In clinical trials of BREYANZI, 35 of 38 patients with a prior history of HBV were treated with concurrent antiviral suppressive therapy. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing. In patients with prior history of HBV, consider concurrent antiviral suppressive therapy to prevent HBV reactivation per standard guidelines.
Prolonged Cytopenias
Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion. In clinical trials of BREYANZI, Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 35% of patients, and included thrombocytopenia in 25%, neutropenia in 22%, and anemia in 6% of patients. Monitor complete blood counts prior to and after BREYANZI administration.
Hypogammaglobulinemia
B-cell aplasia and hypogammaglobulinemia can occur in patients receiving BREYANZI. In clinical trials of BREYANZI, hypogammaglobulinemia was reported as an adverse reaction in 9% of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 30% of patients. Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.
Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI 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 BREYANZI treatment, and until immune recovery following treatment with BREYANZI.
Secondary Malignancies
Patients treated with BREYANZI may develop secondary malignancies. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol-Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing.
Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome (IEC-HS)
Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome (IEC-HS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. Seven out of 769 (0.9%) patients with R/R NHL exposed to BREYANZI developed IEC-HS. Time to onset of IEC-HS ranged from 7 to 32 days. Of the 7 patients, 3 patients developed IEC-HS with overlapping occurrence of CRS and neurotoxicity, 2 patients developed IEC-HS with overlapping occurrence of neurotoxicity, and 1 patient developed IEC-HS with overlapping occurrence of CRS. IEC-HS was fatal in 2 of 7 patients. One patient had fatal IEC-HS and one had ongoing IEC-HS at time of death. IEC-HS is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of IEC-HS should be administered per current practice guidelines.
Adverse Reactions
The most common adverse reaction(s) (incidence ≥30%) in:
LBCL are fever, CRS, fatigue, musculoskeletal pain, and nausea. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decrease, neutrophil count decrease, platelet count decrease, and hemoglobin decrease.
CLL/SLL are CRS, encephalopathy, fatigue, musculoskeletal pain, nausea, edema, and diarrhea. The most common Grade 3-4 laboratory abnormalities include neutrophil count decrease, white blood cell decrease, hemoglobin decrease, platelet count decrease, and lymphocyte count decrease.
FL is CRS. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decrease, neutrophil count decrease, and white blood cell decrease.
MCL are CRS, fatigue, musculoskeletal pain, and encephalopathy. The most common Grade 3-4 laboratory abnormalities include neutrophil count decrease, white blood cell decrease, and platelet count decrease.
MZL is CRS. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decrease, neutrophil count decrease, and white blood cell decrease.
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.
(Press release, Bristol-Myers Squibb, DEC 8, 2025, View Source [SID1234661250])