TRANSFORM
A Global Randomized Multicenter Phase 3 Trial of JCAR017 Compared to Standard of Care in Adult Subjects With High-risk, Second-line, Transplant-eligible Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphomas
Phase 3N = 184NCT03575351
- Population
- Adults aged 18 to 75 years with primary refractory or early relapsed (within 12 months) large B-cell lymphoma, candidates for autologous HSCT.
- Design
- Open-label, randomised (1:1) phase 3 study at 47 sites in the USA, Europe and Japan. Adults aged 18 to 75 years with primary refractory or early relapsed (within 12 months) large B-cell lymphoma, ECOG performance status 1 or less, PET-positive disease and eligible for autologous HSCT were assigned to liso-cel or to three cycles of salvage immunochemotherapy (R-DHAP, R-ICE or R-GDP) followed by high-dose chemotherapy and autologous HSCT in responders. Primary end point: event-free survival with responses assessed by independent review committee per Lugano 2014. 232 patients were screened and 184 randomised. The first report is a prespecified interim analysis.
- Primary endpoint
- EFS
- Arms
- Standard of care (control, n = 92): Three cycles of salvage immunochemotherapy (R-DHAP, R-ICE or R-GDP) followed by high-dose chemotherapy and autologous HSCT in responders
- Lisocabtagene maraleucel (experimental, n = 92): Liso-cel 100 million CAR-positive T cells intravenously
- People
- Kamdar M, senior author Abramson JS
EFSHR 0.35 (95% CI 0.23–0.53)Δ median EFS+7.8 monthsEFSHR 0.375 (95% CI 0.259–0.542)Δ median EFS+27.1 monthsOSHR 0.757 (95% CI 0.481–1.191)Δ 36-month OS+11 points
Show the numbers
| Endpoint | Analysis | Lisocabtagene maraleucel | Standard of care | Effect |
|---|---|---|---|---|
| EFSEvent-free survival with response assessments by independent review committee per Lugano 2014 (stated primary endpoint). | interimmedian follow-up 6.2 monthsKamdar 2022 | median 10.1 months | median 2.3 months (2.2–4.3) | HR 0.35 (95% CI 0.23–0.53)P<0.0001Stratified hazard ratio; stratified Cox proportional hazards model, one-sided p value. The 95% CI for the liso-cel median was 6.1 to not reached, which the schema cannot hold. Data cut-off 8 March 2021. |
| EFSRandomised patients (184); 66% of patients crossed over to receive liso-cel in the overall survival analysisEvent-free survival; results reported descriptively. | long term-updatemedian follow-up 33.9 monthsKamdar 2025 | median 29.5 months | median 2.4 months (2.2–4.9) | HR 0.375 (95% CI 0.259–0.542)Results are reported descriptively. The 95% CI for the liso-cel median was 9.5 to not reached. Median progression-free survival was not reached for liso-cel (12.6 to not reached) versus 6.2 months (4.3 to 8.6) for standard of care, HR 0.422 (95% CI 0.279 to 0.639), 36-month rates 51% versus 26.5%. |
| OSRandomised patients (184); 66% of patients crossed over to receive liso-cel | long term-updatemedian follow-up 33.9 monthsKamdar 2025 | 63% at 3 y | 52% at 3 y | HR 0.757 (95% CI 0.481–1.191)Median overall survival was not reached in either arm; results reported descriptively. The overall survival hazard ratio accounting for the treatment effect of crossover was 0.566 (95% CI 0.359 to 0.895). |
| Endpoint | Analysis | Lisocabtagene maraleucel | Standard of care | Effect |
|---|---|---|---|---|
| EFSEvent-free survival with response assessments by independent review committee per Lugano 2014 (stated primary endpoint). | interimmedian follow-up 6.2 monthsKamdar 2022 | median 10.1 months | median 2.3 months (2.2–4.3) | HR 0.35 (95% CI 0.23–0.53)P<0.0001Stratified hazard ratio; stratified Cox proportional hazards model, one-sided p value. The 95% CI for the liso-cel median was 6.1 to not reached, which the schema cannot hold. Data cut-off 8 March 2021. |
| EFSRandomised patients (184); 66% of patients crossed over to receive liso-cel in the overall survival analysisEvent-free survival; results reported descriptively. | long term-updatemedian follow-up 33.9 monthsKamdar 2025 | median 29.5 months | median 2.4 months (2.2–4.9) | HR 0.375 (95% CI 0.259–0.542)Results are reported descriptively. The 95% CI for the liso-cel median was 9.5 to not reached. Median progression-free survival was not reached for liso-cel (12.6 to not reached) versus 6.2 months (4.3 to 8.6) for standard of care, HR 0.422 (95% CI 0.279 to 0.639), 36-month rates 51% versus 26.5%. |
| OSRandomised patients (184); 66% of patients crossed over to receive liso-cel | long term-updatemedian follow-up 33.9 monthsKamdar 2025 | 63% at 3 y | 52% at 3 y | HR 0.757 (95% CI 0.481–1.191)Median overall survival was not reached in either arm; results reported descriptively. The overall survival hazard ratio accounting for the treatment effect of crossover was 0.566 (95% CI 0.359 to 0.895). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| EFS | 0.35 | 0.23–0.53 |
| EFS | 0.375 | 0.259–0.542 |
| OS | 0.757 | 0.481–1.191 |
- Standard of care (control)
- Lisocabtagene maraleucel (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Standard of care | Lisocabtagene maraleucel |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 6 | 16.4% | 66.2% |
| 13 | 2.0% | 41.0% |
| 19 | 0.3% | 27.1% |
| 25 | 0.1% | 18.0% |
- Standard of care (control)
- Lisocabtagene maraleucel (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Standard of care | Lisocabtagene maraleucel |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 18 | 0.6% | 65.5% |
| 37 | 0.0% | 41.9% |
| 55 | 0.0% | 27.5% |
| 74 | 0.0% | 17.6% |
Appears in
Sources
Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, 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, Johnston PB, Glass B, Bachanova V, 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. J Clin Oncol. 2025;43(24):2671-2678.