Expert Insights: Long-Term Efficacy of Cilta-cel from CARTITUDE-1

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The 5-year follow-up from CARTITUDE-1 revealed remarkable durability with 33% of heavily pretreated patients remaining alive and progression-free. The original study enrolled 97 patients with at least 3 prior lines of therapy who were double refractory to proteasome inhibitors and immunomodulatory drugs. With a median follow-up of 61.3 months, the results far exceed expected outcomes based on the LocoMMotion-1 registry study, which showed 4.6 months median progression-free survival for similar patients receiving standard therapies.

Twelve patients underwent annual bone marrow assessments and PET-CT scans, with all remaining MRD-negative and in complete metabolic response at 5 years postinfusion. Analysis of long-term remitters vs early progressors revealed that lower disease burden at baseline was the key differentiating factor, with median bone marrow plasmacytosis of 5% vs 24% and soluble B-cell maturation antigen levels of 36 vs 58.5, respectively. High-risk cytogenetics and extramedullary disease were equally distributed between groups.

The median overall survival of 60.7 months compared with an expected 12.4 months represents a 5-fold improvement. T-cell product characteristics, including more immune-fit profiles and better effector-to-target ratios, correlated with superior long-term outcomes. These data support a working definition of cure as MRD-negativity with negative PET-CT imaging off all therapy for 5 or more years, though longer follow-up is needed to validate this definition.