{"entity":{"id":"paper-transform-liso-cel-lancet-2022","kind":"paper","name":"TRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=TRANSFORM%20lisocabtagene%20maraleucel%20second-line%20Kamdar%20Lancet%202022"},{"label":"ClinicalTrials.gov NCT03575351","url":"https://clinicaltrials.gov/study/NCT03575351"}],"tags":[],"related":["car-t-before-transplant-lbcl","paper-zuma-7-axi-cel-second-line-nejm-2022","lymphoma-roadmap","paper-belinda-tisagenlecleucel-second-line-nejm-2022","paper-transcend-nhl-001-liso-cel-lancet-2020"],"cancers":["dlbcl"],"sections":[],"technologies":["car-t","autologous-stem-cell-transplant"],"targets":["cd19"],"drugs":["lisocabtagene-maraleucel"],"companies":["bms"],"institutions":[],"pathways":[],"terms":["efs","crs","icans"],"trials":["transform","zuma-7","belinda"],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-toxicity-qol"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2022,"doi":"10.1016/S0140-6736(22)00662-6","pmid":"35717989","authors":"Kamdar M, Solomon SR, Arnason J, et al.","paperType":"rct","findings":["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."],"whatItMeans":"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.","caveats":["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."],"changedPractice":true,"participants":184},"route":"/key-papers/paper-transform-liso-cel-lancet-2022/","neighbours":{"pairing":[{"id":"car-t-before-transplant-lbcl","kind":"pairing","name":"Early relapse: CAR-T before transplant","route":"/pairings/car-t-before-transplant-lbcl/"}],"paper":[{"id":"paper-transcend-nhl-001-liso-cel-lancet-2020","kind":"paper","name":"Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study","route":"/key-papers/paper-transcend-nhl-001-liso-cel-lancet-2020/"},{"id":"paper-belinda-tisagenlecleucel-second-line-nejm-2022","kind":"paper","name":"Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma","route":"/key-papers/paper-belinda-tisagenlecleucel-second-line-nejm-2022/"},{"id":"paper-zuma-7-axi-cel-second-line-nejm-2022","kind":"paper","name":"ZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early","route":"/key-papers/paper-zuma-7-axi-cel-second-line-nejm-2022/"}],"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"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","route":"/roadmaps/lymphoma-roadmap/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"}],"technology":[{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","route":"/technologies/autologous-stem-cell-transplant/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"}],"target":[{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"}],"drug":[{"id":"lisocabtagene-maraleucel","kind":"drug","name":"Lisocabtagene maraleucel","route":"/drugs/lisocabtagene-maraleucel/"}],"company":[{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"}],"term":[{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"},{"id":"efs","kind":"term","name":"Event-free / disease-free survival (EFS, DFS, iDFS, RFS)","route":"/terms/efs/"},{"id":"icans","kind":"term","name":"ICANS (neurotoxicity)","route":"/terms/icans/"}],"trial":[{"id":"belinda","kind":"trial","name":"BELINDA","route":"/trials/belinda/"},{"id":"transform","kind":"trial","name":"TRANSFORM","route":"/trials/transform/"},{"id":"zuma-7","kind":"trial","name":"ZUMA-7","route":"/trials/zuma-7/"}],"bottleneck":[{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"lancet","kind":"journal","name":"The Lancet","route":"/journals/lancet/"}]}}