# CARTITUDE-4: cilta-cel CAR-T versus standard combinations after one to three prior lines of myeloma therapy

Source: https://onco.cc/key-papers/paper-cartitude-4-cilta-cel-nejm-2023/  
OnCo record `paper-cartitude-4-cilta-cel-nejm-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Moving BCMA CAR-T to the second line cut the risk of progression or death by 74% compared with standard triplets, and later improved overall survival.

## Summary

CARTITUDE-4 randomised 419 patients with lenalidomide-refractory multiple myeloma after one to three prior lines to a single infusion of ciltacabtagene autoleucel (after bridging therapy) or standard of care (pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone). The primary endpoint was PFS by intention to treat. At 12 months PFS was 75.9% versus 48.6% (hazard ratio 0.26); overall response was 84.6% versus 67.3%, complete response or better 73.1% versus 21.8%, and MRD-negativity 60.6% versus 15.6%. In later follow-up overall survival was significantly better with cilta-cel (hazard ratio about 0.55). Toxicity was manageable, with lower CRS and neurotoxicity rates than in CARTITUDE-1.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2023
- DOI: 10.1056/NEJMoa2303379
- Authors: San-Miguel J, Dhakal B, Yong K, et al.
- Findings: 419 lenalidomide-refractory patients after 1-3 prior lines; cilta-cel vs PVd or DPd.; 12-month PFS 75.9% vs 48.6%; hazard ratio 0.26 (intention-to-treat).; Complete response or better 73.1% vs 21.8%; MRD-negativity 60.6% vs 15.6%.; Overall survival significantly improved at second analysis (HR about 0.55).; CRS in 76% of infused patients (grade 3-4 about 1%); ICANS about 5%; cranial nerve palsy and movement disorders in a small minority.
- What it means: CARTITUDE-4 is the first randomised trial to show that a CAR-T improves survival in myeloma, and it moved cilta-cel into second-line use (FDA approval 2024). For patients whose disease returns after first-line lenalidomide, a one-off cell therapy now competes with continuous drug combinations. Capacity, cost and the need for bridging therapy still limit who actually receives it.
- Caveats: Open-label; standard-of-care arm was a mix of two regimens, neither of which is the strongest available.; Intention-to-treat analysis includes patients who progressed during bridging; per-protocol PFS is even more favourable.; Only about 15% of standard-arm patients later received CAR-T, so the comparison is partly CAR-T now versus never.; Secondary haematological malignancies and late neurotoxicity remain concerns.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa2303379
- ClinicalTrials.gov NCT04181827: https://clinicaltrials.gov/study/NCT04181827

## Connected records

- key papers: [CARTITUDE-1: cilta-cel, a BCMA CAR-T, in heavily pretreated myeloma](https://onco.cc/key-papers/paper-cartitude-1-cilta-cel-lancet-2021/), [KarMMa-3: ide-cel CAR-T versus standard regimens in triple-class-exposed relapsed myeloma](https://onco.cc/key-papers/paper-karmma-3-ide-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: [Bortezomib](https://onco.cc/drugs/bortezomib/), [Ciltacabtagene autoleucel](https://onco.cc/drugs/ciltacabtagene-autoleucel/), [Daratumumab](https://onco.cc/drugs/daratumumab/), [Pomalidomide](https://onco.cc/drugs/pomalidomide/)
- companies: [Johnson & Johnson](https://onco.cc/companies/johnson-johnson/), [Legend Biotech](https://onco.cc/companies/legend-biotech/)
- terms: [Cytokine release syndrome (CRS)](https://onco.cc/terms/crs/), [MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶)](https://onco.cc/terms/mrd-negativity-myeloma/), [Overall survival (OS)](https://onco.cc/terms/os/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- trials: [CARTITUDE-4](https://onco.cc/trials/cartitude-4/), [CARTITUDE-5](https://onco.cc/trials/cartitude-5/)
- bottlenecks: [Manufacturing cost and time for living and radioactive medicines](https://onco.cc/bottlenecks/b-manufacturing-cell-therapy/), [Most of the world has almost no cancer care](https://onco.cc/bottlenecks/b-global-access/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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