Early Treatment Failure in Patients Receiving Ciltacabtagene‐Autoleucel for Relapsed/Refractory Multiple Myeloma

Ciltacabtagene autoleucel (cilta-cel) has demonstrated excellent efficacy and long-term disease control in patients with relapsed/refractory multiple myeloma (RRMM). However, a proportion of patients experience early treatment failures. We investigated clinical factors associated with early progression or death (within 12 months) in patients with RRMM receiving standard-of-care cilta-cel across the three Mayo clinic centers. Patients with a follow-up of at least 12 months or progression or death within 12 months from infusion were included. Of the patients with early treatment failure (n = 52), 69% had progressive disease and 31% had a non-relapse mortality (NRM) event. In patients without early treatment failure (n = 164), 13% of events were NRM. Among pretreatment factors, prior BCMA-directed therapy, presence of extramedullary disease and a CAR-HEMATOTOX score of ≥ 2 were independent predictors of early progression or death. The utilization of cilta-cel in earlier lines of treatment (1-3 vs. 4 or more) demonstrated comparable PFS (12-month PFS 73% vs. 77%, p = 0.94). Measurable residual disease positivity in the bone marrow at 3 months (11/197 patients) identified a small but high-risk group with an increased risk of early treatment failure (OR 5.68; p = 0.012). Patients with less than a complete response on a FDG PET/CT at 3 months also had an increased risk of early treatment failure (OR 11.8; p < 0.0001). Our findings may help identify patients at high-risk for early adverse outcomes despite receiving highly effective therapy, and support consideration of novel therapeutic strategies within a clinical trial setting.