A Phase 3, randomized, open-label, multicenter, pivotal trial (N=184)

TRANSFORM trial: THE ONE to evaluate Breyanzi® head-to-head vs standard therapy in 2L LBCL patients who were R/R ≤12 months and potential candidates for transplant1,2

Standard therapy in the TRANSFORM trial was immunochemotherapy followed by high-dose therapy + HSCT1

  • Primary endpoint: EFS (evaluated at 6.2 months median follow-up)1,3
  • Select secondary endpoints (evaluated at primary analysis): CR rate, PFS, OS, ORR, and DOR2
  • For the interim analysis, median follow-up was 6.2 months3
  • For the primary analysis, median follow-up was 17.5 months2
  • Bridging therapy prior to receiving lymphodepleting chemotherapy was permitted, and patients in the standard therapy arm were allowed to cross over to the Breyanzi arm1,2

EVENT-FREE SURVIVAL

Breyanzi: THE ONE with 62% reduction in risk of EFS events at a median 3 years post follow-up3,4

Over 4x improvement in mEFS: At 6.2 months follow-up, mEFS was 10.1 months for Breyanzi vs 2.3 months for standard therapy3*†

At 33.9 months median follow-up, mEFS was 29.5 months for Breyanzi vs 2.4 months for standard therapy.4

Event-free survival Kaplan-Meier curve for patients with 2L LBCL at median 3 years follow-up of Breyanzi vs standard therapy

EFS is defined as the time from randomization to death from any cause, progressive disease, failure to achieve CR or PR by 9 weeks post randomization, or the start of new lymphoma therapy due to efficacy concerns, whichever occurs first.1

*Based on a stratified Cox proportional hazards model.3

†P<0.0001; P-value is compared with 0.012 of the allocated alpha for this prespecified interim analysis.1

‡Per the Lugano criteria, as assessed by an IRC.3

§Rates at 3 years (36 months).4

PROGRESSION-FREE SURVIVAL

Breyanzi: THE ONE with PFS benefit over 50% sustained through 3 years4

More than 50% of patients survived without progression at 3-year follow-up, meaning mPFS was not reached3,4*†

Progression-free survival Kaplan-Meier curve for patients with 2L LBCL at median 3 years follow-up of Breyanzi vs standard therapy

PFS is defined as the time from randomization to progressive disease or death from any cause, whichever occurs first.3

*Interim 6.2 months median follow-up: mPFS 14.8 months for Breyanzi vs 5.7 months for standard therapy, P=0.0001.3

†Based on a stratified Cox proportional hazards model.4

‡Rates at 3 years (36 months).4

OVERALL SURVIVAL

Breyanzi: THE ONE with 63% of patients alive at 3 years4

Reduction in the risk of death was 24% (HR: 0.76)4

Overall survival Kaplan-Meier curve for patients with 2L LBCL at median 3 years follow-up of Breyanzi vs standard therapy

OS was a secondary endpoint of TRANSFORM2

Analysis limitations2:

  • At primary analysis, OS was not statistically significant
  • Data were limited for OS because of the number of patient deaths and were based on the ITT principle
  • Estimates were not adjusted for patient crossover

*Rates at 3 years (36 months).4

OVERALL SURVIVAL SUPPORTIVE ANALYSIS

Breyanzi: THE ONE CAR T with crossover in transplant-eligible patients1,3,5*

63% (n=57) of standard therapy patients crossed over to receive Breyanzi2

Overall Kaplan-Meier curve adjusted for crossover, for patients with 2L LBCL of Breyanzi vs standard therapy

Analysis limitations:

  • At primary analysis, OS was not statistically significant
  • Supportive OS analysis was intended to isolate the reflective effect of Breyanzi vs standard therapy without subsequent anticancer therapy
  • OS for standard therapy was estimated based on the outcome if crossover had not occurred

*In TRANSFORM, overall survival in the ITT set and sensitivity analysis were evaluated using a 2-stage accelerated failure time model in order to estimate the survival outcome for the standard therapy arm in a hypothetical scenario where crossover did not occur.5

2L, second-line; CAR, chimeric antigen receptor; CI, confidence interval; CR, complete response; DOR, duration of response; EFS, event-free survival; HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; IRC, Independent Review Committee; ITT, intent-to-treat; LBCL, large B-cell lymphoma; mEFS, median event-free survival; mOS, median overall survival; mPFS, median progression-free survival; NR, not reached; ORR; overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; R/R, relapsed or refractory.

 

Breyanzi: THE ONE to bring the power of CAR T to patients with 2L LBCL, offering the opportunity for deep and durable remission in 74% of patients4

74% of patients achieved deep and durable complete response at 33.9 months median follow-up, and mDOR was not reached4*

Graph showing response rates of Breyanzi in TRANSFORM trial compared to standard therapy

Breyanzi median DOR: NR (95% CI: 16.9, NR); HR: 0.6 (95% CI: 0.4, 1.0)4

Standard therapy median DOR: 9 months (95% CI: 5.1, NR)4

*Interim 6.2 months median follow-up: CR of 66% for Breyanzi vs 39% for standard therapy; P<0.0001.1,3

†Per the Lugano criteria, as assessed by an IRC.1

‡Cochran-Mantel-Haenszel test.1

2L, second-line; CAR, chimeric antigen receptor; CI, confidence interval; CR, complete response; DOR, duration of response; EFS, event-free survival; HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; IRC, Independent Review Committee; LBCL, large B-cell lymphoma; mDOR, median duration of response; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; R/R, relapsed or refractory.

TRANSFORM trial2

Trial design of Breyanzi TRANSFORM clinical trial
  • Primary endpoint (evaluated at interim analysis): EFS1,3
  • Select secondary endpoints (evaluated at primary analysis): CR rate, PFS, OS, ORR, and DOR2

Trial design was patient-centric, allowing for crossover to the Breyanzi arm from
the standard therapy arm2

Patients receiving standard therapy treatment were allowed to receive Breyanzi if they failed to achieve CR or PR after 3 cycles of salvage immunochemotherapy, or had disease progression at any time, or absence of CR 18 weeks after randomization.2

TRANSFORM trial design and patient disposition

Breyanzi arm (N=92)1

Patients randomized to Breyanzi were to receive lymphodepleting chemotherapy consisting of fludarabine 30 mg/m2/day and cyclophosphamide 300 mg/m2/day concurrently for 3 days followed by Breyanzi infusion 2 to 7 days after completion of lymphodepleting chemotherapy. Breyanzi planned dose of 100 × 106 CAR+ T cells.

Bridging chemotherapy was permitted between leukapheresis and the start of lymphodepleting chemotherapy.

  • Of 92 patients randomized to receive Breyanzi, 89 (97%) received Breyanzi
  • 58 (63%) patients received bridging therapy
  • 1 (1.1%; manufacturing failure) patient received a nonconforming product

Standard therapy arm (N=92)1,2

  • Of the 92 patients randomized to receive standard therapy, 91 started treatment and 43 (47%) received high-dose therapy and HSCT
  • The most common reason for not receiving HSCT was lack of efficacy of the salvage chemotherapy
  • 63% (58/92) of patients received crossover treatment with Breyanzi

21% of Breyanzi patients were treated in an outpatient setting per
physicians' discretion1

Breyanzi: THE ONE studied in patients you are likely to see in your practice1,3

Select baseline demographics in the TRANSFORM trial1,3

Characteristics (N=184)
Median age; range 59 years; 20-75 years
ECOG PS 0/1 at screening 57%/43%
Primary refractory‡ 73%
Relapsed§ 27%
LBCL subtypes  
DLBCL, NOS 55%
High-grade B-cell lymphoma 23%
Primary mediastinal large B-cell lymphoma 10%
DLBCL transformed from indolent lymphoma 8%
Secondary CNS involvement 2%

*Standard therapy consisted of 3 cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT in patients who attained CR or PR.2

†Lymphodepleting chemotherapy regimen consisted of fludarabine 30 mg/m2/day and cyclophosphamide 300 mg/m2/day.1

‡Defined as stable disease, progressive disease, PR, or CR with relapse <3 months after first-line therapy.3

§Defined as CR with relapse on or after 3 months within 12 months after first-line therapy.3

2L, second-line; CAR, chimeric antigen receptor; CNS, central nervous system; CR, complete response; DLBCL, diffuse large B-cell lymphoma; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; EFS, event-free survival; HDT, high-dose therapy; HSCT, hematopoietic stem cell transplantation; LBCL, large B-cell lymphoma; LDC, lymphodepleting chemotherapy; NOS, not otherwise specified; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; R/R, relapsed or refractory; SCT, stem cell transplantation.

References

  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2025.
  2. Abramson J, Solomon S, Arnason J, et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study. Blood. 2023;141(14):1675-1684.
  3. Kamdar M, Solomon S, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399(10343):2294-2308.
  4. Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care for second-line relapsed/refractory large B-cell lymphoma: 3-year follow-up from the randomized, phase III TRANSFORM study. Data supplement. J Clin Oncol. Published online July 7, 2025. doi:10.1200/JCO-25-00399
  5. Abramson J, Solomon S, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma: 3-year follow-up of TRANSFORM. Presented at: European Hematology Association Congress; June 13,16, 2024; Madrid, Spain. Presentation S272.

Important Safety Information

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.

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 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 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 34% 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 3.7%, 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 10% 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. 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, cytokine release syndrome, 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.

Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.

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2009-US-2500226

09/2025