3356 - Early Experience with Salvage RT for Relapsed / Refractory Multiple Myeloma Following BCMA-Directed CAR T Cell Therapy

A. Dreyfuss¹, B. Fregonese², S. Mailankody³, S. Usmani⁴, B. S. Imber¹, and J. Yahalom²; ¹Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ²Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ³Memorial Sloan Kettering Cancer Center, New York, NY, ⁴Hematology, Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s): Despite impressive response rates, relapse after chimeric antigen T cell receptor therapy (CART) for Multiple Myeloma (MM) is common, potentiating the need for salvage strategies. Radiation therapy (RT) may be a useful component of salvage, however, the role of RT and integration and sequencing with other systemic therapies have not been well characterized. Here we report on the first cohort of MM patients treated at a large cancer center with salvage RT post-CART progression. Materials/

Methods: MM patients treated with BCMA-directed CART products (52% with experimental, 48% with commercial) between 2017-2022 were identified, and all 21 who received RT to 35 sites post-CART relapse were analyzed. Radiographic response to RT was assessed according to the Lugano or RECIST criteria. Kaplan Meier survival analysis was performed and differences between groups were assessed by log-rank and Pearson’s X² test.
Results: All patients (median age at RT 61 years, range [44-77]) were heavily pre-treated with a median of 7 (3-13) lines of therapy prior to CART and 9 (4-14) prior to salvage RT, with 18 (86%) having high risk cytogenetics, 18 (86%) undergoing 1 stem cell transplant (SCT) prior to RT, and 14 (67%) receiving prior RT. Median time from CART to RT was 6.7 (1.0-42.6) months, time from CART failure to RT was 2.5 (0.1-34.2) months, and follow up post-RT was 4.1 (0.0-67.4) months. RT was used for first post-CART relapse in 10 (48%) patients and for 10 (29%) CART-refractory lesions, and 10 (48%) patients received systemic therapy within 2 weeks of RT. RT indication was definitive salvage for 10 (46%) patients with limited relapse (LR) (<3 sites on imaging), all of whom received comprehensive RT to a median 30 Gy (20-44) in 10 (4-22) fractions. The remaining 11 (54%) patients received RT for symptom palliation to a lower median dose of 20 Gy (8-30) in 5 (1-10) fractions (p<0.001). Overall (OS) (p=0.030) and progression-free survival (PFS) (p=0.010) were significantly better in LR vs widespread relapse. Among LR patients, dose was not associated with OS/PFS. Clinical response was seen in all symptomatic patients, and 93% of irradiated lesions had radiographic response at 1.6 (0.2-8.1) months post-RT, with 1 in-field failure at 5.9 months. Only 1 patient with LR was alive and disease free at analysis, as distant failure occurred in 12 (57%), and 8 (38%) died prior to evaluation. Post-RT, 14 (67%) patients received additional systemic therapy, with 2 undergoing SCT.
Conclusion: RT as a component of salvage post-CART failure can be used in multiple ways with or without concurrent systemic therapy, providing effective symptom palliation and local control, and contributing to overall disease control in patients with LR. Although extent of relapse was prognostic, outcomes in this rapidly growing group is still challenging, suggesting the need for more intensive, multi-modality salvage particularly for these patients.