Data presentations highlight BMS’ leadership and commitment to harnessing the full potential of cell therapy, with advances in blood cancers and beyond
Multiple analyses underscore durable efficacy and well-established safety profile of Breyanzi® (lisocabtagene maraleucel; liso-cel) in leukemia and several types of lymphoma
Expanded pipeline data across multiple modalities feature first survival results for a GPRC5D-directed CAR T, arlocabtagene autoleucel (arlo-cel; BMS-986393), and updated results from a Phase 1 study reinforcing potential of CD19 NEX-T® (BMS-986353) to deliver immune ‘reset’ among patients with severe refractory lupus
PRINCETON, N.J.--(BUSINESS WIRE)--$BMY #ASH--Bristol Myers Squibb (NYSE: BMY) announced results from 18 presentations reinforcing its leadership in cell therapy, with data demonstrating efficacy, durability and safety of currently available therapies in blood cancers and highlighting the potential of its pipeline for future indications including autoimmune diseases. These results, covering a breadth of potential targets within an expanding range of disease areas, were presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California.
“Cell therapy is one of the fastest-growing modalities across our industry, and we’re committed to unlocking its full potential to deliver transformative treatments to patients with cancer and beyond,” said Anne Kerber, senior vice president, head of late clinical development, Hematology, Oncology and Cell Therapy (HOCT), Bristol Myers Squibb. “Our data on Breyanzi and Abecma at ASH reaffirm how our approved CAR T cell therapies continue to demonstrate favorable long-term outcomes, while results from our pipeline offer potential to address the unmet needs of patients with relapsed or refractory multiple myeloma and severe refractory autoimmune diseases.”
Key presentations include:
- Long-term analyses reinforcing the durable efficacy and well-established safety profile of Breyanzi® (lisocabtagene maraleucel; liso-cel) in large B-cell lymphoma (LBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
- New circulating tumor DNA (ctDNA) data from the Phase 3 TRANSFORM study supporting the superiority of Breyanzi to achieve deeper responses over the former standard of care in second-line LBCL
- New analysis highlighting global manufacturing capability, reliability and timely delivery for Abecma® (idecabtagene vicleucel; ide-cel) in relapsed or refractory multiple myeloma (RRMM)
- First overall and progression-free survival data for arlocabtagene autoleucel (arlo-cel; BMS-986393), a GPRC5D-directed CAR T cell therapy in RRMM
- Updated Phase 1 data for CD19 NEX-T® CAR T cell therapy (BMS-986353/CC-97540), highlighting its potential to make a meaningful impact for patients with severe, refractory autoimmune diseases including systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathies, and multiple sclerosis
“We’re excited to disclose the progress of our robust pipeline, with promising early survival results for our GPRC5D-targeted cell therapy underscoring the first-in-class potential of arlocabtagene autoleucel for patients with relapsed or refractory multiple myeloma,” said Bryan Campbell, senior vice president, Head of Global Program Leaders, HOCT, Bristol Myers Squibb. “Beyond blood cancers, we’re encouraged by the continued results we are seeing with CD19 NEX-T in autoimmune diseases, like severe lupus, highlighting its possibility as a one-time treatment to provide sustained and treatment-free remission.”
Breyanzi Phase 1 TRANSCEND NHL Study Results: Abstract #3125
Five-year overall survival (OS) data from the Phase 1 TRANSCEND NHL 001 study support the deep and durable responses of Breyanzi in patients with relapsed or refractory LBCL (R/R LBCL) with median OS of 27.5 months (95% CI: 16.2–47.3) and an estimated OS rate at 5 years of 38% (95% CI: 32-45), with patients who achieved a complete response (CR) having the longest OS. The median disease-specific survival (DSS) was 67.8 months (95% CI: 23.5 - not reached) and estimated DSS rate at 5 years was 52% (95% CI: 45-59). Breyanzi continued to demonstrate an established safety profile with no new safety signals.
Breyanzi Phase 3 TRANSFORM Study Results: Abstract #72
New ctDNA data from the Phase 3 TRANSFORM study support ctDNA as an early predictor of durable clinical benefit after second-line LBCL treatment with Breyanzi. Patients with undetectable ctDNA in the Breyanzi vs standard of care (SOC) arm had longer event-free survival (EFS) at all predefined time points and had statistically longer EFS at Day 126 which corresponds to post-transplant visit for SOC arm (SOC vs Breyanzi: HR, 3.89 [95% CI: 1.43–10.58]). Among patients who achieved both CR and undetectable ctDNA at Day 126 in the study, Breyanzi provided significantly greater EFS benefit vs SOC (SOC vs Breyanzi in patients with CR and undetectable ctDNA: HR, 6.68 [95% CI: 2.11‒21.19]), supporting a deeper and more durable response with Breyanzi vs SOC. These data underscore the role of ctDNA as a biomarker of response in LBCL and support the superiority of Breyanzi to achieve deeper responses over SOC in second-line LBCL.
Breyanzi Real-World Outcomes in Second-Line LBCL: Abstract #470 and Abstract #472
Real-world data from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry supported the use of Breyanzi as a second-line salvage therapy and autologous stem cell transplant in R/R LBCL regardless of age, including for younger (under 70 years) and older patients (70 years and older). At a median follow-up of 6.4 months (95% CI: 6.1-6.5; range, 0.2-14.8), overall response rate (ORR) and CR rate in the overall cohort (n=156) were 84% (95% CI: 77–89) and 70% (95% CI: 62-77), respectively. TRANSFORM-ineligible patients (n=105) had an ORR of 84% (95% CI: 75-90) and CR rate of 68% (95% CI: 58–76), while those who might have been eligible (n=51) had an ORR of 84% (95% CI: 71–93) and CR rate of 75% (95% CI: 60-86). Median duration of response (DOR), progression-free survival (PFS), and OS were not reached. The safety profile remained predictable, with cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) reported in 45% and 20% of patients, respectively.
Additionally, real-world data from the CIBMTR Registry supported the use of Breyanzi as a feasible and effective therapeutic option in real-world patients with R/R LBCL and secondary Central Nervous System (sCNS) involvement. At a median follow up of 12 months (95% CI: 1-24), ORR was 73% (95% CI: 60%–84%) and the CR rate was 64% (95% CI: 50%–77%). The CR rate in this population was similar to that observed in the overall population in the TRANSCEND NHL 001 (NCT02631044) study despite all patients in this study having sCNS involvement. The safety profile of Breyanzi in patients with sCNS was manageable and consistent with pivotal trials and prior real-world reports. CRS, mostly low grade, was reported in 60% of patients, and 58% did not experience any ICANS.
Breyanzi Phase 2 TRANSCEND FL Study Results: Abstract #4387
After two years of follow-up, patients with third-line-plus and second-line high-risk relapsed or refractory follicular lymphoma (R/R FL) who received a single administration of Breyanzi had ORR and CR rates above 94%. For third-line-plus patients, 24-month DOR, PFS and OS were 74.6% (95% CI: 64.8-82.1), 72.5% (95% CI: 62.7-80.1), and 88.2% (95% CI: 80.1-93.1), respectively. For 2L patients, 24-month DOR, PFS and OS were 86.4% (95% CI: 63.4-95.4), 82.6% (95% CI: 60.1-90.3), and 95.7% (95% CI: 72.9-99.4), respectively. Breyanzi continued to demonstrate a safety profile consistent with the primary analysis, with no new safety signals. These data support Breyanzi as a durable and safe treatment option for patients with R/R FL.
Breyanzi Phase 1/2 TRANSCEND CLL 004 Study Results: Abstract #887
Primary analysis results from the Breyanzi plus ibrutinib combination cohort of the Phase 1/2 TRANSCEND CLL 004 trial showed that treatment with Breyanzi plus ibrutinib, a Bruton tyrosine kinase inhibitor (BTKi), resulted in deep remissions (86% ORR [95% CI: 74-94], 45% CR [95% CI: 31-60] rate, and 86% undetectable measurable residual disease (MRD) [95% CI: 74-94] rate in blood), as well as an established safety profile in patients with R/R CLL/SLL. Grade ≥ 3 treatment emergent adverse events (TEAEs) occurred in 48 (86%) of patients, most commonly neutropenia (52%) and anemia (41%), with no Grade 5 TEAEs. The data support this novel combination as a promising therapeutic strategy for patients with R/R CLL/SLL.
Global Manufacturing Results for Abecma: Abstract #3476
A new analysis of 4,117 RRMM patients who underwent leukapheresis for commercial Abecma between February 23, 2021, and May 1, 2024, as captured on the Cell Therapy 360® portal, found that the overall manufacturing success rate (MSR) for Abecma was 96.8% and that the MSR rate improved over 3 years (95.8%, 96.4%, 97.2%, and 98.0% in 2021, 2022, 2023 and 2024, respectively). In addition, the analysis showed consistency in commercial MSR across geographies in 2024 (97.7%, 98.3% and 98.0% in the US, EU and Japan, respectively). These results reinforce the commercial manufacturing reliability for Abecma and ability to meet the increasing global patient demand.
First Disclosure of Phase 1 Efficacy and Safety Results of arlocabtagene autoleucel (BMS-986393): Abstract #922
In an oral presentation, BMS showcased the first OS and progression-free survival (PFS) data for arlo-cel, a GPRC5D-targeted CAR T therapy. In the Phase 1 study, patients had three or more prior anti-multiple myeloma regimens including a proteasome inhibitor, an immunomodulatory agent, and anti-CD38 therapy. After a median follow-up of 16.1 months (range, 2.8-25.2) in efficacy-evaluable patients (n= 79), arlo-cel demonstrated durable responses, with ORR maintained at 87%. MRD was evaluated as an exploratory endpoint, and 57% (48/84) of patients were MRD-evaluable. Results showed that 46% (22/48) of patients were MRD-negative and had a CR/stringent CR (sCR). In all treated patients, 27% (23/84) were MRD-negative and achieved a CR. Median PFS was 18.3 months (95% CI: 11.8-21.9) and median OS was not reached. Treatment-related adverse events (TRAEs), specifically hematological adverse events (AEs), were most common in patients, with neutropenia occurring in 62 (74%) patients. Overall, 69 patients (82%) had CRS. Three patients had macrophage activation syndrome/hemophagocytic lymphohistiocytosis, and ICANS occurred in eight patients. Safety data showed on-target/off-tumor AEs were low frequency, low severity, and mostly self-resolving.
These data support arlo-cel being investigated as a potential first-in-class treatment for heavily pretreated RRMM and its ongoing evaluation in the Phase 2 QUINTESSENTIAL study (NCT06297226).
Updated Data of Phase 1 Study of CD19-Directed CAR T BMS-986353: Abstract #2088
Updated data were presented from a Phase 1 study of CD19 NEX-T (BMS-986353) highlighting the promising efficacy and safety in patients with severe, refractory autoimmune diseases. Safety results were presented for 17 patients, including 2 patients with relapsing-remitting multiple sclerosis (MS), 3 patients with system sclerosis (SSc), 1 patient with idiopathic inflammatory myopathies (IIM), and 11 patients with systemic lupus erythematosus (SLE). In efficacy-evaluable patients with SLE (n=7), significant improvements in Systemic Lupus Erythematosus Disease Activity Index (median score reduction of 10 points at 1 month following BMS-986353 infusion) and Physician Global Assessment (median score reduction of 82% at 1 month following BMS-986353 infusion) were observed, and all patients remained off all autoimmune-directed therapies without evidence of disease flare. Results showed manageable initial safety in patients with autoimmune diseases. CRS was reported in 1 patient with SLE (Grade 1) and 1 patient with SSc (Grade 2), for a duration of one day. ICANS was reported in 1 patient with SSC (Grade 1) and 1 patient with SLE (Grade 3), with a median duration of 3 days. There were no prolonged Grade ≥3 cytopenias or dose-limiting toxicities reported.
These results highlight the potential of BMS-986353 as a one-time infusion of CD19-directed CAR T cell therapy to reset the immune systems of patients with autoimmune diseases, which may provide treatment-free sustained remission.
Bristol Myers Squibb thanks the patients and investigators participating in these cell therapy clinical trials.
Please see the Important Safety Information section below, including Boxed WARNINGS for Breyanzi and Abecma.
About TRANSCEND NHL 001
TRANSCEND NHL 001 (NCT02631044) is an open-label, multicenter, pivotal, Phase 1, single-arm, seamless-design study to determine the safety, pharmacokinetics and antitumor activity of Breyanzi in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, follicular lymphoma Grade 3B and mantle cell lymphoma. The primary outcome measures are treatment-related adverse events, dose-limiting toxicities and overall response rate. Secondary outcome measures include complete response rate, duration of response, and progression-free survival.
About TRANSFORM
TRANSFORM (NCT03575351) is a pivotal, global, randomized, multicenter Phase 3 trial evaluating Breyanzi compared to current standard therapy regimens (platinum-based salvage chemotherapy followed by high-dose chemotherapy and HSCT in patients responding to salvage chemotherapy) in patients with large B-cell lymphoma (LBCL) that was primary refractory or relapsed within 12 months after CD20-antibody and anthracycline containing first-line therapy. Patients were randomized to receive Breyanzi or standard of care salvage therapy, including rituximab plus dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP), rituximab plus ifosfamide, carboplatin and etoposide (R-ICE), or rituximab plus gemcitabine, dexamethasone and cisplatin (R-GDP) per the investigators’ choice before proceeding to high-dose chemotherapy (HDCT) and hematopoietic stem cell transplant (HSCT). The primary endpoint of the study was event-free survival (EFS), defined as time from randomization to death from any cause, progressive disease, failure to achieve complete response or partial response, or start of new antineoplastic therapy due to efficacy concerns, whichever occurs first. Complete response (CR) rate was a key secondary endpoint. Other efficacy endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and duration of response (DOR).
About TRANSCEND CLL 004
TRANSCEND CLL 004 (NCT03331198) is a Phase 1/2 open-label, single-arm, multicenter study evaluating Breyanzi in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. The Phase 1 dose escalation portion of the study assessed the safety and recommended dose for the subsequent Phase 2 expansion cohort. The phase 1 dose-escalation portion includes cohorts assessing liso-cel monotherapy and liso-cel combined with ibrutinib. The Phase 2 portion of the study is evaluating Breyanzi at the recommended dose from the Phase 1 monotherapy arm. The primary endpoint of the Phase 2 portion of the study is complete response rate, including complete remission with incomplete bone marrow recovery, based on independent review committee according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines.
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.
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, and for the treatment of relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma after at least two prior lines of therapy, and for the treatment of relapsed or refractory follicular lymphoma in adult patients who have received two or more prior lines of systemic therapy, and for the treatment of relapsed or refractory mantle cell lymphoma in patients who have received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. Breyanzi is also approved in Japan and Europe for the second-line treatment of relapsed or refractory LBCL, and in Japan, Europe, Switzerland and Canada for relapsed and refractory LBCL after two or more lines of systemic therapy.
Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in other types of lymphoma. For more information, visit clinicaltrials.gov.
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.
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.
- BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.
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 702 patients with non-Hodgkin lymphoma (NHL), CRS occurred in 54% of patients, including ≥ Grade 3 CRS in 3.2% of patients. The median time to onset was 5 days (range: 1 to 63 days). CRS resolved in 98% 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, tachycardia, chills, 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 31% 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 days (range: 1 to 119 days). Of patients developing neurotoxicity, 82% also developed CRS.
The most common neurologic toxicities (≥5%) included encephalopathy, tremor, aphasia, headache, dizziness, and delirium.
CRS and Neurologic Toxicities Monitoring
Monitor patients daily for at least 7 days following BREYANZI infusion at a REMS-certified healthcare facility for signs and symptoms of CRS and neurologic toxicities and assess for other causes of neurological symptoms. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 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. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time.
BREYANZI REMS
Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:
- Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
- Certified healthcare facilities must have on-site, immediate access to tocilizumab.
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