TRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma
In TRANSFORM, a second CD19 CAR-T, lisocabtagene maraleucel, also beat chemotherapy-plus-transplant as second-line treatment, with a low rate of severe side effects.
TRANSFORM randomised 184 patients with large B-cell lymphoma refractory to or relapsed within 12 months of first-line therapy to lisocabtagene maraleucel (liso-cel) or standard salvage chemotherapy with autologous transplant for responders. Bridging chemotherapy was allowed and crossover to liso-cel was permitted for standard-arm failures. The primary endpoint was event-free survival. At the interim analysis median EFS was 10.1 versus 2.3 months (hazard ratio 0.35) with complete response 66% versus 39%; in the primary analysis median EFS was not reached versus 2.4 months (hazard ratio 0.36). Grade 3 CRS occurred in 1% and grade 3 neurological events in 4%. Overall survival was not significantly different, in part because of crossover.
- 184 patients with primary refractory or early-relapsing LBCL; liso-cel vs salvage chemotherapy and transplant.
- Interim: median EFS 10.1 vs 2.3 months; hazard ratio 0.35; complete response 66% vs 39%.
- Primary analysis: median EFS not reached vs 2.4 months; hazard ratio 0.36.
- Grade 3 CRS 1%; grade 3 neurological events 4%; no grade 4-5 CRS or neurotoxicity.
- Crossover to liso-cel allowed; OS not significantly different.
TRANSFORM confirmed ZUMA-7's conclusion with a different CD19 CAR-T and a more permissive design that allowed bridging chemotherapy, making the results closer to real-world practice. Liso-cel's low toxicity makes it attractive for older or frailer patients and for outpatient delivery. Together the two trials made CAR-T the standard second-line therapy for early-relapsing aggressive lymphoma.
- Smaller than ZUMA-7 and reported at interim analysis; EFS rather than OS was the endpoint.
- Crossover blunted any survival comparison.
- Excludes late relapse.
- Liso-cel manufacturing involves separate CD4 and CD8 components, adding complexity.