Background
Phase II multicohort single-arm study; Cohort C, N=20 with relapsed/refractory multiple myeloma progressing despite a PI, IMiD, anti-CD38 antibody, and prior non-cellular anti-BCMA therapy (ADC or bispecific). Tested ciltacabtagene autoleucel (cilta-cel), anti-BCMA CAR T, after prior BCMA exposure.
Interventions and follow up
Treatment: Lymphodepletion (cyclophosphamide/fludarabine) followed by a single infusion of ciltacabtagene autoleucel (target 0.75×10^6 CAR+ cells/kg).
Primary endpoint: Minimal residual disease (MRD) negativity at 10^-5.
mFollow up: 11.3 months.
Primary endpoint: Minimal residual disease (MRD) negativity at 10^-5.
mFollow up: 11.3 months.
Results
MRD negativity (10^-5): 7/20 (35%) overall; 7/10 (70.0%) in the MRD-evaluable subset.
ORR: 60.0% (95% CI 36.1–80.9).
DOR: median 11.5 months (95% CI 7.9–NE).
PFS: median 9.1 months (95% CI 1.5–NE).
OS: NR.
ORR: 60.0% (95% CI 36.1–80.9).
DOR: median 11.5 months (95% CI 7.9–NE).
PFS: median 9.1 months (95% CI 1.5–NE).
OS: NR.
Adverse events
CRS: 12 patients (60%), all grade 1–2.
Neurotoxicity (ICANS): 4 patients, 2 grade 3–4; no parkinsonism reported.
Hematologic: Most common adverse events were cytopenias.
Deaths: 7 (35%) — 3 progressive disease, 4 adverse events (1 treatment-related).
Neurotoxicity (ICANS): 4 patients, 2 grade 3–4; no parkinsonism reported.
Hematologic: Most common adverse events were cytopenias.
Deaths: 7 (35%) — 3 progressive disease, 4 adverse events (1 treatment-related).
Conclusions
Cilta-cel produced an ORR of 60% in heavily pretreated patients largely refractory to prior non-cellular anti-BCMA therapy, supporting activity even after prior BCMA-targeting exposure, though responses were less deep and durable than in BCMA-naive populations.
Key Limitations
Small single-arm cohort (N=20) with short follow-up and no comparator. Responses shallower/less durable than cilta-cel in BCMA-naive patients. Optimal sequencing of CAR T after prior BCMA-directed bispecifics/ADCs remains undefined.
Clinical Context
Cilta-cel is FDA- and EMA-approved for relapsed/refractory myeloma (CARTITUDE-1/-4). Cohort C informs the clinically pressing question of CAR T efficacy after prior BCMA-directed therapy as bispecifics enter earlier lines; ESMO/IMWG sequencing guidance increasingly emphasizes BCMA-target rotation.