TRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma · Key paper

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.

Randomised controlled trialChanged practice184 participants

Authors

Kamdar M, Solomon SR, Arnason J, et al.

Published

The Lancet, 2022

What it found

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.

What it means

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.

Be careful

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.

Key papers

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rctNew England Journal of Medicine 2022changed practice

ZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early

ZUMA-7 rewrote second-line treatment for aggressive lymphoma: patients whose disease returns within a year of R-CHOP should be offered CAR-T rather than salvage chemotherapy and transplant. It is also one of the few cell-therapy trials to show an overall survival benefit despite crossover. Patients relapsing later than 12 months were not studied and transplant remains standard for them if chemosensitive.