Background/Objectives: Systemic therapies for multiple myeloma (MM) have advanced considerably, changing the landscape of MM treatment paradigms. 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 use, outcomes, and the impact of RT on radiographic and biochemical markers, with genomic characterization for more recently treated patients.

Materials/Methods: 506 pathologically confirmed MM patients who received RT to 1190 sites between 1/1/2000 and 6/1/2022 were identified. Patient, disease, and treatment characteristics were analyzed for 50 consecutive patients treated in 2019 (recent sampling but with reasonable follow for analysis) and tested for association with cumulative incidence of 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 (Memorial Sloan Kettering IMPACT).

Results: Among the 50 patients analyzed (median 63 years), 90 lesions were treated with RT, 33% with concurrent systemic therapy, to a 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. Pre-RT PET imaging was performed in a majority of patients (62%). With a 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. Of the patients with DF, 93% had sustained local control of the irradiated site. Absolute decreases 1-week to 1-month post-RT were observed in marrow plasma cell percentage, (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%).

Conclusion: In this pilot analysis of a sampling cohort of RT-treated MM, we report on patterns of utilization, outcomes, and biochemical and radiographic correlates. Ultimately, 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. At the meeting, we will present data from a larger cohort of MM patients, with further sub-analyses on the relevance of baseline imaging to subsequent irradiated lesions, as well as toxicity and outcomes data with the use of radiotherapy in conjunction with newer systemic agents (bi-specific antibodies and chimeric antigen receptor T-cell therapy).

Usmani:Array Biopharma: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Research Funding; TeneoBio: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; SkylineDX: Membership on an entity's Board of Directors or advisory committees, Research Funding; K36 Therapeutics: Membership on an entity's Board of Directors or advisory committees; SecuraBio: Membership on an entity's Board of Directors or advisory committees; Moderna: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; EdoPharma: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Imber:GT Medical Technologies: Honoraria. Yahalom:Convergent R.N.R Ltd.: Other: Provision of Services (uncompensated).

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2023
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