1121 - Patterns of Failure in Multiple Myeloma with Extramedullary Disease Following Anti-BCMA Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy

J. Y. Nakashima¹, V. M. Khatri¹, R. J. Cruz-Chamorro¹, J. Zhou², P. Patra², R. Gonzalez³, G. De Avila³, F. L. Locke³, H. D. Liu³, T. Nishihori³, O. C. Puglianini³, M. Alsina³, A. Garjales-Cruz⁴, R. Baz⁴, B. D. Shah⁴, K. Shain⁴, M. D. Jain³, D. Hansen³, C. Freeman³, and N. B. Figura¹; ¹H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, ²University of South Florida, Tampa, FL, ³H. Lee Moffitt Cancer Center and Research Institute, Department of Blood and Marrow Transplant and Cellular Immunotherapy, Tampa, FL, ⁴H. Lee Moffitt Cancer Center and Research Institute, Department of Malignant Hematology, Tampa, FL

Purpose/Objective(s): Anti B-cell maturation antigen (BCMA) directed CAR T-cell therapy has revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM). Early evidence suggests that patients with extramedullary disease (EMD) experience inferior clinical outcomes to CAR. We aim to measure the clinical outcomes of RRMM patients with EMD and analyze their patterns of failure following CAR. Materials/

Methods: We identified all RRMM patients who received anti-BCMA CAR at our institution from 2021 to 2023. Baseline patient characteristics, prior treatments, and clinical outcomes are recorded in a prospectively managed database. Pretreatment PET/CTs were reviewed to identify patients with EMD, defined as either paraskeletal plasmacytomas (PSPs) or soft tissue plasmacytomas (STPs). Each pretreatment plasmacytoma was individually contoured for future lesion-level radiomic analysis. Patterns of failure analysis was performed by comparing the disease distribution at time of progression to pretreatment scan. Recurrent sites of EMD were categorized as a local or distant failure. Time-to-event outcomes were estimated using Kaplan-Meier method and compared with log-rank tests.
Results: We identified 116 RRMM patients who underwent BCMA CAR, of which 30 (25.8%) had pretreatment EMD. The presence of EMD was associated with drastically inferior outcomes (12-month PFS 60.2% vs. 15.6%, p<0.001). The 30 patients with EMD had a median age of 60 (38-78), 6 (4-9) prior lines of therapy, and a median of 3 (1-6) plasmacytomas on pretreatment PET. Twenty (67%) had strictly STPs, three (10%) had strictly PSPs, while seven (23%) had evidence of both. The majority (24, 80%) underwent bridging systemic therapy while seven had bridging radiotherapy (RT). None received bridging RT to a site of EMD. 25 patients received ide-cel while five received cilta-cel. At a median follow-up of 19.5 months, 90% of EMD patients experienced disease progression translating to a median PFS and OS of 3.1 and 15.7 months, respectively. At time of progression, 17 (57%) patients had evidence of recurrent EMD, where 10 had biochemical relapse alone. Twelve patients with recurrent EMD had a local failure while 2 patients experienced strictly local failures. While nearly all EMD patients eventually recur, those with local EMD failure had an inferior duration of response to cellular therapy (6-month PFS 45.5% vs 25.0%, p=0.04).
Conclusion: While anti-BCMA CAR has revolutionized the treatment for RRMM, patients with pretreatment EMD have significantly inferior clinical outcomes. In this high-risk cohort, a substantial proportion will progress in a known site of EMD. Furthermore, those with local EMD failure experience a shorter duration of treatment response to cellular therapy. Given the high rates of local failures, locally directed therapies, such as bridging RT, may be a potential treatment strategy to improve treatment outcomes.