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For lymphoma that came back within a year, going straight to CAR-T beat the decades-old chemotherapy-then-transplant approach, and later improved survival.
ZUMA-7 randomised 359 patients with large B-cell lymphoma that was refractory to, or relapsed within 12 months of, first-line chemo-immunotherapy to axicabtagene ciloleucel (axi-cel) or standard second-line salvage chemotherapy followed by high-dose therapy and autologous transplant in responders. The primary endpoint was event-free survival. Median EFS was 8.3 versus 2.0 months (hazard ratio 0.40) and 24-month EFS 41% versus 16%; complete response was 65% versus 32%. Only about a third of standard-arm patients reached transplant, and 56% went on to receive CAR-T off protocol. Despite that crossover, the later analysis (Westin et al., NEJM 2023) showed improved overall survival with axi-cel (4-year OS 54.6% versus 46.0%; hazard ratio 0.73).
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.
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.
ZUMA-1 showed that CAR-T can cure a meaningful fraction of adults whose aggressive lymphoma no longer responds to chemotherapy, a group with a historical median survival of about six months (SCHOLAR-1). Axi-cel became the first CAR-T approved for lymphoma and later the first to beat standard second-line therapy in ZUMA-7. The comparatively high neurotoxicity of CD28-costimulated products was also first characterised here.
Shares BELINDA, ZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma, Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma, ICANS (neurotoxicity).
Shares BELINDA, TRANSFORM, Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma, ZUMA-7.
Shares TRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma, Report the time from apheresis to infusion as a trial endpoint, not a logistics footnote, TRANSFORM, ZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma.
Shares BELINDA, Report the time from apheresis to infusion as a trial endpoint, not a logistics footnote, TRANSFORM, ZUMA-7.
Shares BELINDA, TRANSFORM, ZUMA-7, ICANS (neurotoxicity).
Shares BELINDA, Report the time from apheresis to infusion as a trial endpoint, not a logistics footnote, TRANSFORM, Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma.
Shares ZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma, ZUMA-7, Axicabtagene ciloleucel, CD19.
Shares ZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma, ICANS (neurotoxicity), Gilead Sciences (incl. Kite), Cytokine release syndrome (CRS).