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% |
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
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*†
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
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
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*
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
- 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
*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
- Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2025.
- 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.
- 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.
- 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
- 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.