Background
Phase 1b/2, open-label, single-arm trial (CARTITUDE-1). N=97 patients with relapsed or refractory multiple myeloma after ≥3 prior lines (median 6) including a PI, IMiD, and daratumumab (triple-class exposed). Ciltacabtagene autoleucel (cilta-cel; JNJ-68284528) is an autologous BCMA-directed CAR-T with two BCMA-binding domains designed for enhanced avidity.
Interventions and follow up
Regimen: Ciltacabtagene autoleucel (cilta-cel) 0.75 × 10⁶ CAR-T cells/kg IV (single infusion) after fludarabine 30 mg/m² + cyclophosphamide 300 mg/m² daily ×3 lymphodepletion
Population: Triple-class–exposed R/R MM
Primary endpoint: Overall response rate (ORR)
mFollow up: 12.4 months
Population: Triple-class–exposed R/R MM
Primary endpoint: Overall response rate (ORR)
mFollow up: 12.4 months
Results
ORR: 97.9% (95% CI 92.7–99.7%)
≥CR rate: 67.0%
Stringent CR (sCR): 28.6%
MRD-negativity (10⁻⁵): 93.0% (among evaluable)
12-mo PFS rate: 76.6%; mPFS NR at 12.4-month follow-up
≥CR rate: 67.0%
Stringent CR (sCR): 28.6%
MRD-negativity (10⁻⁵): 93.0% (among evaluable)
12-mo PFS rate: 76.6%; mPFS NR at 12.4-month follow-up
Adverse events
CRS/neurotoxicity: CRS any grade 94.8%, grade ≥3 4.1%; ICANS any grade 20.6%, grade ≥3 7.2%; delayed Parkinsonism/movement disorders in 4.1% (novel CAR-T toxicity distinct from ICANS)
Hematologic (grade ≥3): Neutropenia 95.8%, anemia 67.9%, thrombocytopenia 59.7%
Hematologic (grade ≥3): Neutropenia 95.8%, anemia 67.9%, thrombocytopenia 59.7%
Conclusions
Cilta-cel achieved an unprecedented 97.9% ORR with 67% ≥CR and 93% MRD-negativity in heavily pretreated triple-class-exposed RRMM, establishing the highest response rates ever reported for a CAR-T cell therapy in myeloma.
Key Limitations
Small single-arm cohort (N=97) without a randomized comparator; short follow-up at primary analysis (mPFS not reached). Delayed neurotoxicity, including movement and neurocognitive disorders, emerged as a serious novel safety signal requiring prophylaxis and intensive monitoring. Manufacturing failures and vein-to-vein time excluded some patients. Near-universal grade ≥3 cytopenias demand specialized supportive care.
Clinical Context
FDA approved cilta-cel (Carvykti) in February 2022 for RRMM after ≥4 prior lines; CARTITUDE-4 later supported earlier-line use. Risk-mitigation strategies (early cytokine intervention, neurotoxicity prophylaxis) substantially reduced delayed neurotoxicity in subsequent trials. ESMO-MCBS reflects high benefit in an unmet-need setting.