# KarMMa-3: ide-cel CAR-T versus standard regimens in triple-class-exposed relapsed myeloma

Source: https://onco.cc/key-papers/paper-karmma-3-ide-cel-nejm-2023/  
OnCo record `paper-karmma-3-ide-cel-nejm-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2023
- DOI: 10.1056/NEJMoa2213614
- Authors: Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al.
- 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.
- What it means: 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.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa2213614
- ClinicalTrials.gov NCT03651128: https://clinicaltrials.gov/study/NCT03651128

## Connected records

- key papers: [CARTITUDE-4: cilta-cel CAR-T versus standard combinations after one to three prior lines of myeloma therapy](https://onco.cc/key-papers/paper-cartitude-4-cilta-cel-nejm-2023/)
- cancers: [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Relapsed or refractory multiple myeloma](https://onco.cc/cancers/myeloma-relapsed-refractory/)
- technologies: [CAR-T cell therapy](https://onco.cc/technologies/car-t/)
- targets: [BCMA](https://onco.cc/targets/bcma/)
- drugs: [Idecabtagene vicleucel](https://onco.cc/drugs/idecabtagene-vicleucel/)
- companies: [Bristol Myers Squibb](https://onco.cc/companies/bms/)
- terms: [Cytokine release syndrome (CRS)](https://onco.cc/terms/crs/), [Objective response rate (ORR)](https://onco.cc/terms/orr/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- trials: [KarMMa-3](https://onco.cc/trials/karmma-3/)
- bottlenecks: [Manufacturing cost and time for living and radioactive medicines](https://onco.cc/bottlenecks/b-manufacturing-cell-therapy/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- people: [Nikhil C. Munshi](https://onco.cc/people/nikhil-munshi/), [Noopur Raje](https://onco.cc/people/noopur-raje/)

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