Radiation in a New Era of Multiple Myeloma Management: Patterns of Utilization, Clinical, Radiologic, and Biochemical Outcomes, and Possible Genomic Correlates of Response

Abstract

Systemic therapies for multiple myeloma (MM) have advanced considerably, improving patient outcomes. Yet, the use of radiotherapy (RT) has remained heterogeneous, and even controversial, due to minimal data on outcomes. With the ultimate goal of guiding the design of prospective trials incorporating RT, we initiated a study of our institutional experience treating MM with RT since 1/1/2000. Here we report a preliminary feasibility analysis of an initial sample cohort, identifying patterns of RT utilization, outcomes, and impact of RT on radiographic and biochemical markers, with genomic characterization for more recently treated patients. Five hundred six pathologically confirmed MM patients who received RT to 1190 sites between January 1, 2000, and June 1, 2022, were identified. Patient, disease, and treatment characteristics were analyzed for 50 consecutive patients treated in 2019 and tested for association with local and distant failure (LF, DF) using univariable and multivariable analysis. Genomic data was obtained via next generation sequencing using an institutional targeted sequencing panel. Amongthe 50 patients analyzed (median 63 years), 90 lesions were treated with RT, 33% with concurrent systemic therapy, to median dose of 20 Gy (8-46 Gy) over a median of 5 fractions (1-25). RT Indications were pain (56%), critical structure involvement (25%), peri-operative (9%), salvage/consolidation (8%), and bridging therapy (2%). Median size of RT-treated lesions was 4.2 cm (1.4-7.9) and included non-vertebral bones (62%), spine (24%), and extramedullary sites (14%). The median number of lines of pre-RT therapy was 7 (1-14) and 51% had >9 lesions on imaging, 47% involving both medullary and extramedullary sites. With median follow-up of 12.4 months (0.5-46), LF occurred in 5% of treated sites and 89% had DF, most commonly in both medullary + extramedullary (51.4%) sites. Absolute decreases 1-week to 1-month post-RT were observed in % of marrow plasma cell (median 4.0%), M spike (0.30 g/dL), total protein (0.3 g/dL), K:L ratio (0.01), lesion size (1.5cm), and lesion SUV (3.1) but in this limited sample, none were significantly associated with disease control. A cohort of 62 RT-treated MM patients from 2016-2022 had genomic data available; most common tumor mutations were in TP53 (35%), HIST1 (34%), NRAS (34%), and KRAS (23%). In this pilot analysis of a sampling cohort of RT-treated MM, we report on patterns of utilization, outcomes, and biochemical and radiographic correlates. At the meeting, we will present the full analysis of the >500 MM patients and further analyze emerging genomic data. We aim to characterize the role of RT in the modern era of systemic therapy to guide the design of future prospective trials and to inform novel approaches for incorporating RT into the treatment paradigm.