1087 - Fast Forward: Hypofractionated, Dose De-escalated Radiotherapy for Multiple Myeloma

05:20pm - 05:25pm ET

Room 162

Presenter(s)

Alok Deshane, MD - MSKCC, New York, NY

A. Deshane¹, A. Dreyfuss², B. Fregonese¹, G. Cederquist¹, Z. R. Moore¹, B. S. Imber¹, and J. Yahalom¹; ¹Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ²Department of Radiation Oncology, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL

Purpose/Objective(s):

Radiotherapy (RT) provides effective palliation and local control for relapsed Multiple Myeloma (MM). NCCN and ILROG guidelines suggest regimens ranging from 8-30 Gy in 1-10 fractions (fx), yet few comparative data exist to guide dose selection. For indolent B cell lymphomas, PET-adapted dose de-escalation enables many patients (pts) to receive short course, low dose RT without compromised outcomes. Abbreviated RT courses for MM are attractive due to potential reduced toxicity and systemic therapy (ST) disruptions. We hypothesized that 12 Gy/3 fx could achieve comparable local control to standard regimens such as 20 Gy/5 fx. Since MM lacks established PET response criteria, we also explored if metabolic response was associated with local failure (LF).

Materials/Methods:

We prospectively treated 50 consecutive MM pts with 12 Gy/3 fx between 02/2024 and 12/2025. We collected pt characteristics, disease features, including cytogenetics, and prior ST. We analyzed pre-RT lesion characteristics including diameter, SUV, and anatomic classification. Outcomes included metabolic response by Lugano criteria at first post-RT PET, LF (Deauville 5 on any post-RT PET), and freedom from local progression (FFLP). For comparison, we analyzed a historical cohort of pts treated with 20 Gy/5 fx (the former institutional standard) between 2013-22. Chi-square and Mann-Whitney U tests compared categorical and continuous variables, respectively; log-rank testing compared FFLP.

Results:

Of 50 pts treated with 12 Gy/3 fx to 71 sites, 37 pts (treated to 50 sites) had =1 post-RT PET and were analyzed. Pts had a median of 2 prior ST lines and most (28/37, 76%) had high risk cytogenetics. Median pre-RT lesion diameter was 3.4 cm (Range: 0.9 - 10.6) and lesion SUV was 6.5 (1.8 - 53.5). Sites were 18% extramedullary (EM), 46% osseous, and 34% paramedullary. Post-RT PET was performed at a median of 2.1 months (mo) (0.6 – 8.3). Overall response rate (ORR) was 89% and complete response rate (CRR) was 47%. At median follow-up (f/u) of 7.7 mo, 7 sites (14%) had LF.

In the historical cohort, 113 sites received 20 Gy/5 fx, with median f/u of 12 mo. Baseline median lesion diameter (3.4 vs. 4.5 cm, p = 0.052) and SUV (6.5 vs. 7.3, p = 0.37) did not significantly differ between cohorts. The 12 Gy cohort had a higher proportion of EM sites (9/50 vs 4/113, p=0.001). Importantly, CRR (47% vs. 55%, p = 0.36), ORR (89% vs. 85%, p = 0.49), and FFLP (p = 0.31) were similar across groups. Achieving CR was not associated with LF: 9/64 (14%) sites without CR vs. 9/69 (13%) with CR subsequently had LF (p = 0.86).

Conclusion:

Early data suggest that hypofractionated, dose de-escalated RT of 12 Gy/3 fx achieves comparable outcomes to the more standard 20 Gy/5 fx regimen. CRR was low in both cohorts, but CR was not associated with LF. These findings warrant more efforts to identify pt and disease features suitable for shorter course de-escalated RT. Early post-RT PET appeared adequate for future studies of RT integration for MM.