3355 - Radiation Therapy (RT) in a New Era of Multiple Myeloma (MM) Therapy: Trends of Engagement and Radiologic, Biochemical, and Cytogenetic Correlates of Outcomes and Response

A. Dreyfuss¹, B. Fregonese², G. Cederquist², S. Usmani³, 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, ³Hematology, Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s): Systemic therapies for MM have advanced considerably. Yet, the use of RT has remained stagnant due to heterogeneous integration into modern treatments. Here we report on two cohorts of MM RT patients at a large cancer center, assessing trends of RT engagement, radiographic and biochemical outcomes, and potential correlates of RT response. Materials/

Methods: 466 MM patients who received RT to 1165 sites between 2000 – 2022 were identified. 80 consecutive RT courses delivered in 2013-2016 and 2019 were analyzed. Cohorts were compared using the Wilcoxon rank sum test and Pearson X² test. Biomarkers changes were evaluated with a paired sample t-test.
Results: From 2000-2022, the number of RT courses increased to a greater extent than that of MM diagnoses (compounded annual growth rate of 20% vs 10%). Among the 2 groups of 80 RT courses, most common RT indications were palliation or protection of critical sites (89% in 2013-2016, 74% in 2019), but peri-operative RT increased over time (4% to 10%), salvage/consolidative RT doubled (7% to 14%), and bridging RT emerged in 2019 (4%) (p=0.065). Median time from diagnosis to RT was 3.3 years (0.0-15.8) in 2013-2016 and 4.9 years (0.1-22.8) in 2019 (p=0.065), and 75% of patients had PETCT <3 months prior to RT. Compared to 2013-2016, the 2019 cohort received more lines of therapy prior to RT (median 6 (0-14) vs 3 (0-11), p<0.001) and had more lesions on imaging (p=0.013) with more frequent extramedullary disease (EMD) (54% vs 26%, p<0.001), suggesting later use of RT. Dosing and fractionation (p<0.001) and use of concurrent systemic therapy (71% vs 49%, p=0.001) decreased over time while maintaining excellent response rates of 73% and 88% (p=0.211). Interestingly, local failure (LF) (failure in RT field) was low at 10% despite distant failure (DF) occurring in 91%. Still, sustained local control (LC) through last follow up or death was observed in 89% of these patients, and all LF occurred at or after DF (7.9 months, 0.0-39.1). Prior to RT, high risk cytogenetics (t(4:14), del(1p), del(17p), or 1q gain/amplification) were present in all patients who had LF, except for 1 who had an unspecified 14q32.3 rearrangement and 13q deletion only. 74% of LF occurred in patients with EMD pre-RT, and 85% had progressed <18 months post-initial therapy. Decreases post-RT were seen in total plasma protein (3%, p<0.001), lesion size (33%, p<0.001), and SUV (69%, p<0.001).
Conclusion: Analysis of two cohorts of RT-treated MM revealed changes in RT use. We documented the radiographic and biochemical impact of RT, and identified cytogenetic and clinical features that may indicate relative radio-resistance. While sustained LC of irradiated lesions was surprisingly high, further analyses to inform more optimal, possibly earlier incorporation of RT into current treatments are ongoing.