{"entity":{"id":"paper-zuma-2-brexu-cel-mantle-cell-nejm-2020","kind":"paper","name":"ZUMA-2: brexu-cel CAR-T for mantle cell lymphoma that has failed BTK inhibitors","aka":[],"tldr":"In mantle cell lymphoma that had stopped responding to BTK inhibitors, a single CAR-T infusion produced responses in 93% of patients and complete remissions in two-thirds.","summary":"ZUMA-2 was a single-arm phase 2 study of KTE-X19 (brexucabtagene autoleucel), a CD19 CAR-T manufactured with removal of circulating tumour cells, in relapsed or refractory mantle cell lymphoma after up to five prior lines including a BTK inhibitor. Of 74 patients enrolled, 68 received the product. In the primary efficacy analysis of the first 60 treated patients the overall response rate was 93% and complete response 67%; estimated 12-month PFS was 61% and OS 83%. Grade 3 or higher CRS occurred in 15% and neurological events in 31%. It led to FDA approval in 2020, the first CAR-T for mantle cell lymphoma.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1914347"},{"label":"ClinicalTrials.gov NCT02601313","url":"https://clinicaltrials.gov/study/NCT02601313"}],"tags":[],"related":["paper-zuma-1-axi-cel-nejm-2017"],"cancers":["mantle-cell-lymphoma"],"sections":[],"technologies":["car-t"],"targets":["cd19","btk"],"drugs":["brexucabtagene-autoleucel","ibrutinib","pirtobrutinib"],"companies":["gilead"],"institutions":["md-anderson"],"pathways":[],"terms":["crs","icans","orr"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa1914347","authors":"Wang M, Munoz J, Goy A, et al.","paperType":"translational","findings":["74 enrolled, 68 treated; all had prior BTK inhibitor; 60 in primary efficacy analysis.","Overall response 93%; complete response 67%.","Estimated 12-month PFS 61%; 12-month OS 83%.","Grade 3 or higher CRS 15%; grade 3 or higher neurological events 31%.","Responses seen in high-risk features including TP53 mutation and blastoid morphology."],"whatItMeans":"ZUMA-2 gave patients with BTK-inhibitor-refractory mantle cell lymphoma, who previously had a median survival under a year, a therapy with durable remissions in a substantial fraction. Brexu-cel is now standard after BTK inhibitor failure and CAR-T is being tested earlier in the disease. Neurotoxicity rates are higher than in other lymphoma CAR-T trials.","caveats":["Single-arm; no randomised comparison.","High rates of neurological toxicity, and a treatment-related death rate that requires experienced centres.","Later real-world data showed lower complete response rates than the trial.","Long-term durability is limited by late relapses in roughly half of responders."],"changedPractice":true,"participants":68},"route":"/key-papers/paper-zuma-2-brexu-cel-mantle-cell-nejm-2020/","neighbours":{"paper":[{"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/"}],"cancer":[{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"}],"technology":[{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"}],"target":[{"id":"btk","kind":"target","name":"BTK (Bruton tyrosine kinase)","route":"/targets/btk/"},{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"}],"drug":[{"id":"brexucabtagene-autoleucel","kind":"drug","name":"Brexucabtagene autoleucel","route":"/drugs/brexucabtagene-autoleucel/"},{"id":"ibrutinib","kind":"drug","name":"Ibrutinib","route":"/drugs/ibrutinib/"},{"id":"pirtobrutinib","kind":"drug","name":"Pirtobrutinib","route":"/drugs/pirtobrutinib/"}],"company":[{"id":"gilead","kind":"company","name":"Gilead Sciences (incl. Kite)","route":"/companies/gilead/"}],"institution":[{"id":"md-anderson","kind":"institution","name":"MD Anderson Cancer Center","route":"/institutions/md-anderson/"}],"term":[{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"},{"id":"icans","kind":"term","name":"ICANS (neurotoxicity)","route":"/terms/icans/"},{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"person":[{"id":"michael-wang","kind":"person","name":"Michael L. Wang","route":"/people/michael-wang/"}]}}