Early Treatment Failure in Patients Receiving Ciltacabtagene‐Autoleucel for Relapsed/Refractory Multiple Myeloma
Kenneth J. C. Lim, Shaji Kumar, Ricardo Parrondo, Saurabh Chhabra, Melinda Tan, Katharine Dooley, Andre De Menezes Silva Corraes, Morie Gertz, Lisa Hwa, Haily Stephens, Prashant Kapoor, Taxiarchis Kourelis, Rahma Warsame, Joselle Cook, Moritz Binder, Nadine Abdallah, P. Leif Bergsagel, Udit Yadav, J. Erin Wiedmeier‐Nutor, Susan Geyer, S. Vincent Rajkumar, Sikander Ailawadhi, Rafael Fonseca, Yi Lin, Saurabh ZanwarABSTRACT
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.