CARTITUDE-4
Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma (CARTITUDE-4)
Phase 3N = 419NCT04181827
- Population
- Lenalidomide-refractory myeloma after one to three previous lines (including a proteasome inhibitor and an immunomodulatory drug), ECOG performance status 0 or 1.
- Design
- Phase 3, randomized, open-label trial of cilta-cel (apheresis, bridging therapy, lymphodepletion, then a single infusion of 0.75 x 10^6 CAR T cells per kg) versus the physician's choice of pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone. The primary end point was progression-free survival. The primary report is the NEJM paper; the 2026 Lancet Oncology paper is a prespecified second interim analysis of overall survival with an updated progression-free survival analysis.
- Primary endpoint
- PFS
- Arms
- Cilta-cel (experimental, n = 208): Ciltacabtagene autoleucel after bridging therapy and lymphodepletion
- Standard of care (control, n = 211): Pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone
- People
- San-Miguel J, senior author Einsele H
PFSHR 0.26 (95% CI 0.18–0.38)Δ 12-month PFS+27.3 pointsΔ ORR+17.3 pointsOSHR 0.78 (95% CI 0.5–1.2)PFSHR 0.29 (95% CI 0.22–0.39)OSHR 0.55 (95% CI 0.39–0.79)
Show the numbers
| Endpoint | Analysis | Cilta-cel | Standard of care | Effect |
|---|---|---|---|---|
| PFSRandomised patients (419) | primarymedian follow-up 15.9 monthsSan-Miguel 2023 | 75.9% at 12 mo (69.4–81.1%) | median 11.8 months; 48.6% at 12 mo (41.5–55.3%) | HR 0.26 (95% CI 0.18–0.38)P<0.001Median progression-free survival was not reached in the cilta-cel group. Cytokine release syndrome occurred in 76.1% of the 176 as-treated cilta-cel patients (grade 3 or 4, 1.1%). |
| ORRRandomised patients (419) | primarySan-Miguel 2023 | 84.6% | 67.3% | Complete response or better 73.1% versus 21.8%; absence of minimal residual disease 60.6% versus 15.6% (as reported in the abstract). |
| OSRandomised patients (419) | primarySan-Miguel 2023 | — | — | HR 0.78 (95% CI 0.5–1.2)Deaths from any cause in 39 patients (cilta-cel) and 46 patients (standard care); immature at this analysis. |
| PFSITT population | long term-updatemedian follow-up 33.6 monthsEinsele 2026 | — | median 11.8 months (9.7–14.0) | HR 0.29 (95% CI 0.22–0.39)Median progression-free survival was not reached (95% CI 34.5 months to not evaluable) in the cilta-cel group. Maximum grade 4 treatment-emergent adverse events occurred in 156 (75%) patients with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (73% and 54%). |
| OSITT population | interimmedian follow-up 33.6 monthsEinsele 2026 | — | — | HR 0.55 (95% CI 0.39–0.79)P=0.0009Prespecified second interim analysis of overall survival. Median overall survival was not reached with cilta-cel and not reached (95% CI 37.7 months to not evaluable) with standard of care. In the safety population, deaths occurred in 50 (24%) patients with cilta-cel and 82 (39%) with standard of care, including six (3%) and five (2%) due to treatment-related adverse events. |
| Endpoint | Analysis | Cilta-cel | Standard of care | Effect |
|---|---|---|---|---|
| PFSRandomised patients (419) | primarymedian follow-up 15.9 monthsSan-Miguel 2023 | 75.9% at 12 mo (69.4–81.1%) | median 11.8 months; 48.6% at 12 mo (41.5–55.3%) | HR 0.26 (95% CI 0.18–0.38)P<0.001Median progression-free survival was not reached in the cilta-cel group. Cytokine release syndrome occurred in 76.1% of the 176 as-treated cilta-cel patients (grade 3 or 4, 1.1%). |
| ORRRandomised patients (419) | primarySan-Miguel 2023 | 84.6% | 67.3% | Complete response or better 73.1% versus 21.8%; absence of minimal residual disease 60.6% versus 15.6% (as reported in the abstract). |
| OSRandomised patients (419) | primarySan-Miguel 2023 | — | — | HR 0.78 (95% CI 0.5–1.2)Deaths from any cause in 39 patients (cilta-cel) and 46 patients (standard care); immature at this analysis. |
| PFSITT population | long term-updatemedian follow-up 33.6 monthsEinsele 2026 | — | median 11.8 months (9.7–14.0) | HR 0.29 (95% CI 0.22–0.39)Median progression-free survival was not reached (95% CI 34.5 months to not evaluable) in the cilta-cel group. Maximum grade 4 treatment-emergent adverse events occurred in 156 (75%) patients with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (73% and 54%). |
| OSITT population | interimmedian follow-up 33.6 monthsEinsele 2026 | — | — | HR 0.55 (95% CI 0.39–0.79)P=0.0009Prespecified second interim analysis of overall survival. Median overall survival was not reached with cilta-cel and not reached (95% CI 37.7 months to not evaluable) with standard of care. In the safety population, deaths occurred in 50 (24%) patients with cilta-cel and 82 (39%) with standard of care, including six (3%) and five (2%) due to treatment-related adverse events. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.26 | 0.18–0.38 |
| OS | 0.78 | 0.5–1.2 |
| PFS | 0.29 | 0.22–0.39 |
| OS | 0.55 | 0.39–0.79 |
- Standard of care (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Standard of care |
|---|---|
| 0 | 100.0% |
| 7 | 66.3% |
| 15 | 41.4% |
| 22 | 27.5% |
| 30 | 17.2% |
- Standard of care (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Standard of care |
|---|---|
| 0 | 100.0% |
| 7 | 66.3% |
| 15 | 41.4% |
| 22 | 27.5% |
| 30 | 17.2% |
Appears in
Sources
San-Miguel J, Dhakal B, Yong K, Spencer A, Anguille S, Mateos MV, et al. Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. N Engl J Med. 2023;389(4):335-347.
Einsele H, San-Miguel J, Dhakal B, Touzeau C, Leleu X, van de Donk NW, et al. Cilta-cel in lenalidomide-refractory multiple myeloma (CARTITUDE-4): an updated analysis including overall survival from an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2026;27(2):254-268.