10 - Phase II Multi-Institutional Study of Ultralow-Dose (4Gy) Response-Adapted Radiotherapy for Symptomatic Bone Metastases from Multiple Myeloma

Purpose/Objective(s): Palliative radiation therapy (RT) is a critical component of multiple myeloma (MM) care. Given the nature of MM, RT commonly exposes bone marrow to cytotoxic treatment. Data exists showing that a bone marrow dose of 10 Gy causes hematologic toxicity (HT). Since there is no consensus as to the most effective dose for palliation, this study hypothesized that ultralow dose RT (4Gy) could provide a pain response while minimizing HT.

Materials/Methods: This prospective multi-institutional single-arm phase II trial evaluated clinical pain response, both based on the average Brief Pain Inventory (BPI) and oral morphine equivalent dosing (OMED) according to the International Consensus on Palliative RT, in patients who received 4Gy (either 2Gy x 2 or 4Gy x 1) to an uncomplicated painful bone lesion at 4, 8 weeks and 6 months. The primary endpoint was the proportion of patients with self-reported pain response at 4 weeks. Reirradiation with clinician-choice regimens could be considered at =4 weeks following initial treatment for inadequately controlled pain.

Results: 63 evaluable patients with 70 lesions from 7 institutions received 4Gy from 4/2019-9/2025. 29% of patients received 4Gy x 1. 49% were female, with median age of 66 years. 89% had an ECOG performance status 0-1, 79% had prior chemo (median number of lines of therapy was 1), and 40% had prior RT to a different area. The median baseline BPI was 4.8. The median follow-up after RT was 186 days. The pain response rate in those that completed questionnaires at 4 and 8 weeks was 59% and 63% (median BPI and OMED decrease of 2.25, 5mg, and 2.75, 6.2mg, respectively), with pain response of 82% at 6 months. The median time to pain relief was 36 days with a median duration of 148 days. There was no difference in pain relief based on fractionation. 24% of patients received a second course of RT, with a median dose of 20Gy at a median of 71 days after completion of the 4Gy treatment. Following reirradiation, the pain response rate was 63% after 4 weeks with a median time to pain relief of 95 days. There was no grade 3+ treatment related toxicity.

Conclusion: Ultralow dose radiation improved pain and produced durable responses in the majority of patients. The proportion of patients with improved pain increased over time. Notably, relatively few patients required a second course of RT (24%). This response-adapted approach allowed for selective augmentation of pain control with minimal toxicity.