{"entity":{"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","aka":[],"tldr":"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.","summary":"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).","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2116133"},{"label":"Overall survival analysis (Westin 2023)","url":"https://doi.org/10.1056/NEJMoa2301665"},{"label":"ClinicalTrials.gov NCT03391466","url":"https://clinicaltrials.gov/study/NCT03391466"}],"tags":[],"related":["car-t-before-transplant-lbcl","paper-transform-liso-cel-lancet-2022","lymphoma-roadmap","paper-belinda-tisagenlecleucel-second-line-nejm-2022","lymphoma-ev-manufacturing-time-as-a-trial-endpoint"],"cancers":["dlbcl"],"sections":[],"technologies":["car-t","autologous-stem-cell-transplant"],"targets":["cd19"],"drugs":["axicabtagene-ciloleucel"],"companies":["gilead"],"institutions":["moffitt"],"pathways":[],"terms":["efs","os","crs","icans"],"trials":["zuma-7","transform","belinda"],"people":["frederick-locke"],"bottlenecks":["b-manufacturing-cell-therapy","b-global-access"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2116133","authors":"Locke FL, Miklos DB, Jacobson CA, et al.","paperType":"rct","findings":["359 patients with primary refractory or early-relapsing (within 12 months) LBCL; axi-cel vs salvage chemotherapy plus autologous transplant.","Median EFS 8.3 vs 2.0 months; hazard ratio 0.40; 24-month EFS 41% vs 16%.","Overall response 83% vs 50%; complete response 65% vs 32%.","Only 36% of standard-arm patients proceeded to transplant; 56% later received cellular therapy off protocol.","Overall survival improved (4-year OS 54.6% vs 46.0%; HR 0.73), the first survival gain in this setting in decades.","Grade 3 or higher CRS 6%; grade 3 or higher neurological events 21%; no bridging chemotherapy allowed (steroids only)."],"whatItMeans":"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.","caveats":["Applies only to early relapse or primary refractory disease; late relapse was excluded.","No bridging chemotherapy was permitted, so patients with rapidly progressive disease may not have been enrolled.","The parallel BELINDA trial of tisagenlecleucel in the same setting was negative, showing the result depends on product and logistics.","Costs and centre capacity limit uptake outside high-income countries."],"changedPractice":true,"participants":359},"route":"/key-papers/paper-zuma-7-axi-cel-second-line-nejm-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-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-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","route":"/key-papers/paper-transform-liso-cel-lancet-2022/"},{"id":"paper-zuma-1-axi-cel-nejm-2017","kind":"paper","name":"ZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma","route":"/key-papers/paper-zuma-1-axi-cel-nejm-2017/"}],"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/"}],"idea":[{"id":"lymphoma-ev-manufacturing-time-as-a-trial-endpoint","kind":"idea","name":"Report the time from apheresis to infusion as a trial endpoint, not a logistics footnote","route":"/ideas/lymphoma-ev-manufacturing-time-as-a-trial-endpoint/"}],"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":"axicabtagene-ciloleucel","kind":"drug","name":"Axicabtagene ciloleucel","route":"/drugs/axicabtagene-ciloleucel/"}],"company":[{"id":"gilead","kind":"company","name":"Gilead Sciences (incl. Kite)","route":"/companies/gilead/"}],"institution":[{"id":"moffitt","kind":"institution","name":"Moffitt Cancer Center","route":"/institutions/moffitt/"}],"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/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"}],"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/"}],"person":[{"id":"frederick-locke","kind":"person","name":"Frederick L. Locke","route":"/people/frederick-locke/"},{"id":"jason-westin","kind":"person","name":"Jason R. Westin","route":"/people/jason-westin/"}],"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-global-access","kind":"bottleneck","name":"Most of the world has almost no cancer care","route":"/bottlenecks/b-global-access/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}