Bridging therapy response and type as determinants of cilta-cel outcomes in relapsed/refractory multiple myeloma

Abstract

Ciltacabtagene autoleucel (cilta-cel) has demonstrated remarkable efficacy in relapsed/refractory multiple myeloma (RRMM). Bridging therapy (BT) is commonly used to mitigate progression pre-lymphodepletion (LD) and enhance safety and efficacy. However, real-world evidence characterizing BT strategies and outcomes is limited. This retrospective study included patients with RRMM who received commercial cilta-cel (May 2022–January 2025). Biochemical response to BT as well as post-infusion outcomes including cilta-cel response, progression-free survival (PFS), and safety were assessed. Among 192 patients receiving cilta-cel, 172 (90%) received BT. Of 115 patients with evaluable biochemical response to BT, 54% achieved decreased disease, with response highest among talquetamab and proteasome inhibitor-based regimens. Safety was consistent with the known cilta-cel profile. Reduction in disease burden during BT was associated with lower rates of grade ≥ 3 ICANS, while alkylator-based BT had higher rates of grade ≥ 3 cytopenias. Overall response rate to cilta-cel was 92% (69% with at least complete response), with numerically higher rates among those with decreased disease during BT. Median PFS was not reached among patients with decreased disease during BT versus 16.2 months among those with stable/increased disease (p = 0.03). Findings suggest that biochemical response to BT may enhance the benefit-risk profile of cilta-cel in clinical practice.