2L TRANSFORM trial

A Phase 3, randomized, open-label, multicenter, pivotal trial (N=184)1

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

Standard therapy in the TRANSFORM trial was immunochemotherapy followed by high-dose therapy + HSCT1-3
  • Primary endpoint: EFS (evaluated at 6.2 months median follow-up)
  • Select secondary endpoints (evaluated at primary analysis): CR rate, PFS, OS, ORR, DOR
  • For the interim analysis, median follow-up was 6.2 months
  • For the primary analysis, median follow-up was 17.5 months
  • Bridging therapy prior to receiving lymphodepleting chemotherapy was permitted, and patients in the standard therapy arm were allowed to cross over to the Breyanzi arm
EVENT-FREE SURVIVAL
62% reduction in risk of EFS events at a median 3 years post follow-up4,5
Over 4x improvement in mEFS: At 6.2 months median follow-up, mEFS was 10.1 months for Breyanzi vs 2.3 months for standard therapy1,2*†‡
  • At 33.9 months median follow-up, mEFS was 29.5 months for Breyanzi vs 2.4 months for standard therapy2
Graph showing 4x improvement in mEFS over standard therapy.
Graph showing 4x improvement in mEFS over 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
Symbols represent censored observations.
*Based on a stratified Cox proportional hazards model.1
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.1
§Rates at 3 years (36 months).4
PROGRESSION-FREE SURVIVAL
PFS benefit over 50% sustained through 3 years4,5
More than 50% of patients survived without progression at 3-year follow-up, meaning mPFS was not reached4,5*
Graph showing PFS 2x that of standard therapy
Graph showing PFS 2x that of standard therapy
PFS is defined as the time from randomization to progressive disease or death from any cause, whichever occurs first.2
*Interim 6.2-month median follow-up: mPFS 14.8 months for Breyanzi vs 5.7 months for standard therapy, P=0.001.2,3
Based on a stratified Cox proportional hazards model.2
Rates at 3 years (36 months).4
OVERALL SURVIVAL
63% of patients were alive at 3 years4,5
Reduction in the risk of death was 24% (HR: 0.76)4,5
Graph showing percentage of living patients at 2 years
Graph showing percentage of living patients at 2 years
OS was a secondary endpoint of TRANSFORM3
Study limitations:
  • 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
2L, second-line; 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; NR, not reached; mEFS, median event-free survival; mOS, median overall survival; mPFS, median progression-free survival; ORR; overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; R/R, relapsed or refractory.
TRANSFORM trial3
Trial design of TRANSFORM clinical trial Breyanzi
Trial design of TRANSFORM clinical trial Breyanzi
  • Primary endpoint (evaluated at interim analysis): EFS1,3
  • Select secondary endpoints (evaluated at primary analysis): CR rate, PFS, OS, ORR, DOR4
Trial design was patient-centric, allowing for crossover to the Breyanzi arm
from the standard therapy arm4
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 if the patient needed to start a new treatment due to efficacy concerns.4
TRANSFORM trial design and patient disposition1
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
  • Fifty-eight (63%) patients received bridging therapy
  • One (1.1%; manufacturing failure) patient received a nonconforming product
Standard therapy arm (N=92)1,3
  • 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
Choose Breyanzi for patients with 2L LBCL who are R/R ≤12 months and transplant-eligible1
Select baseline demographics in the TRANSFORM trial1,3
Characteristics1,2 (N=184)
Median age, range 59, 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.3
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.
74% of patients achieved deep and durable complete response at 33.9 months median follow-up2*
Graph showing response rates to Breyanzi compared to standard therapy
Graph showing response rates to Breyanzi compared to standard therapy
Breyanzi median DOR: NR (95% CI: 16.9, NR); HR: 0.603 (95% CI: 0.364, 1.000)2
Standard therapy median DOR: 9 months (95% CI: 5.1, NR)2
*Interim 6.2 months medium follow-up: CR of 66% for Breyanzi vs 39% for standard therapy; P<0.0001.3,4
Per the Lugano criteria, as assessed by an IRC.1
Cochran-Mantel-Haenszel test.1
2L, second-line; 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; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; R/R, relapsed or refractory.

This website is best viewed
using the horizontal display on
your tablet device.

This website is best viewed
using the vertical display on
your mobile device.