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The pivotal study of the third CAR-T product for lymphoma, built from a fixed one-to-one mix of two kinds of T cell, with severe immune side effects in only a small minority.
A seamless design study at 14 United States cancer centres in adults with relapsed or refractory large B-cell lymphomas, including diffuse large B-cell lymphoma, high-grade B-cell lymphoma with MYC and BCL2, BCL6 or both rearranged, transformed disease, primary mediastinal B-cell lymphoma and grade 3B follicular lymphoma. Three target dose levels were tested in sequence, each given as a sequential infusion of separately manufactured CD8 and CD4 chimeric antigen receptor positive T cells at equal target doses.
Between 11 January 2016 and 5 July 2019, 344 patients underwent leukapheresis and 269 received at least one dose. Patients had a median of three previous lines, 112 (42 per cent) were 65 or older, 181 (67 per cent) had chemotherapy-refractory disease and seven (3 per cent) had secondary central nervous system involvement. Safety and activity did not differ by dose level, and the recommended target dose was 100 million chimeric antigen receptor positive T cells. Of 256 patients in the efficacy-evaluable set, 186 (73 per cent, 95 per cent confidence interval 66.8 to 78.0) had an objective response and 136 (53 per cent, 46.8 to 59.4) a complete response.
The evidence that made lisocabtagene maraleucel the CD19 CAR-T product most often chosen for older or frailer patients, because its severe cytokine release syndrome rate is a fraction of the other two products'.
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 TRANSFORM, TRANSCEND NHL 001, ICANS (neurotoxicity), Cytokine release syndrome (CRS) and the tag lymphoma-evidence.
Shares Complete response, ICANS (neurotoxicity), Cytokine release syndrome (CRS), Manufacturing cost and time for living and radioactive medicines and the tag lymphoma-evidence.
Shares Complete response, ICANS (neurotoxicity), Cytokine release syndrome (CRS), Manufacturing cost and time for living and radioactive medicines and the tag lymphoma-evidence.
Shares TRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma, TRANSFORM, Report the time from apheresis to infusion as a trial endpoint, not a logistics footnote, Manufacturing cost and time for living and radioactive medicines and the tag lymphoma-evidence.
Shares Complete response, Objective response rate (ORR), Cytokine release syndrome (CRS), Manufacturing cost and time for living and radioactive medicines and the tag lymphoma-evidence.
Shares ICANS (neurotoxicity), Cytokine release syndrome (CRS), Manufacturing cost and time for living and radioactive medicines, CD19 and the tag lymphoma-evidence.
Shares Complete response, Objective response rate (ORR), Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Follicular lymphoma and the tag lymphoma-evidence.
Shares Complete response, Objective response rate (ORR), Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Follicular lymphoma and the tag lymphoma-evidence.