{"entity":{"id":"paper-karmma-3-ide-cel-nejm-2023","kind":"paper","name":"KarMMa-3: ide-cel CAR-T versus standard regimens in triple-class-exposed relapsed myeloma","aka":[],"tldr":"The first randomised CAR-T trial in myeloma tripled median progression-free survival (13.3 versus 4.4 months) compared with standard combinations after two to four prior lines.","summary":"KarMMa-3 randomised 386 patients with relapsed and refractory multiple myeloma after two to four prior lines, including an immunomodulatory drug, a proteasome inhibitor and daratumumab, to idecabtagene vicleucel (ide-cel) or one of five standard regimens. The primary endpoint was PFS. Median PFS was 13.3 versus 4.4 months (hazard ratio 0.49); overall response was 71% versus 42% and complete response 39% versus 5%. CRS occurred in 88% (grade 3 or higher in 5%) and neurotoxicity in 15%. Overall survival did not differ significantly, in part because more than half of standard-arm patients crossed over to ide-cel.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2213614"},{"label":"ClinicalTrials.gov NCT03651128","url":"https://clinicaltrials.gov/study/NCT03651128"}],"tags":[],"related":["paper-cartitude-4-cilta-cel-nejm-2023"],"cancers":["multiple-myeloma"],"sections":[],"technologies":["car-t"],"targets":["bcma"],"drugs":["idecabtagene-vicleucel"],"companies":["bms"],"institutions":[],"pathways":[],"terms":["pfs","orr","crs"],"trials":["karmma-3"],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-trial-design"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2213614","authors":"Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al.","paperType":"rct","findings":["386 patients after 2-4 prior lines, triple-class exposed; ide-cel vs 5 standard regimens (2:1).","Median PFS 13.3 vs 4.4 months; hazard ratio 0.49.","Overall response 71% vs 42%; complete response or better 39% vs 5%.","CRS 88% (grade 3 or higher 5%); investigator-identified neurotoxicity 15% (grade 3 or higher 3%).","No significant OS difference after adjusting for crossover; most standard-arm patients received ide-cel at progression."],"whatItMeans":"KarMMa-3 was the first randomised evidence that CAR-T beats conventional drugs in myeloma and led to ide-cel's approval after two prior lines. It confirmed that earlier use of CAR-T produces deeper and longer remissions than in the end-stage setting. Because responses are shorter than with cilta-cel and OS was not improved, it also sharpened debate about which BCMA CAR-T to use and when.","caveats":["Crossover blunted the OS comparison; a survival benefit could not be shown.","Standard-arm regimens varied and included some now regarded as suboptimal.","Median PFS with ide-cel remains modest compared with cilta-cel in CARTITUDE-4 (indirect comparison).","Manufacturing time and slot availability restrict real-world use."],"changedPractice":true,"participants":386},"route":"/key-papers/paper-karmma-3-ide-cel-nejm-2023/","neighbours":{"paper":[{"id":"paper-cartitude-4-cilta-cel-nejm-2023","kind":"paper","name":"CARTITUDE-4: cilta-cel CAR-T versus standard combinations after one to three prior lines of myeloma therapy","route":"/key-papers/paper-cartitude-4-cilta-cel-nejm-2023/"}],"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"myeloma-relapsed-refractory","kind":"cancer","name":"Relapsed or refractory multiple myeloma","route":"/cancers/myeloma-relapsed-refractory/"}],"technology":[{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"}],"target":[{"id":"bcma","kind":"target","name":"BCMA","route":"/targets/bcma/"}],"drug":[{"id":"idecabtagene-vicleucel","kind":"drug","name":"Idecabtagene vicleucel","route":"/drugs/idecabtagene-vicleucel/"}],"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":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"trial":[{"id":"karmma-3","kind":"trial","name":"KarMMa-3","route":"/trials/karmma-3/"}],"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-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"person":[{"id":"nikhil-munshi","kind":"person","name":"Nikhil C. Munshi","route":"/people/nikhil-munshi/"},{"id":"noopur-raje","kind":"person","name":"Noopur Raje","route":"/people/noopur-raje/"}]}}