Phase II Multi-Institutional Study of a Low-Dose (4 Gy) Palliative Response-Adapted Radiotherapy Regimen for Symptomatic Bone Metastases from Multiple Myeloma: Planned Interim Analysis of First 40 Patients

Abstract

Painful bone lesions are common in patients with multiple myeloma (MM). Radiotherapy (RT) is effective in providing pain relief from MM bone lesions in over 80% of patients. There is no consensus as to the most effective dose or fractionation for palliation. Shorter courses of therapy are not only more convenient for patients, but they also have less impact on timing of systemic therapies. There is precedent for using 4 Gy in the palliation of lymphomas, which have similar radiosensitivity to myeloma. The primary objective of this trial is to determine whether treatment with a total dose of 4 Gy to a painful myeloma bone lesion achieves patient-reported pain reduction comparable to historical controls at 4 weeks. Patients with a known diagnosis of MM and a painful bone lesion that was not at the base of skull, in need of stabilization, or causing cord compression were treated with 4 Gy (2 Gy x 2 or 4 Gy x 1). Patients' pain was measured using the brief pain index (BPI) prior to treatment and at 2, 4, 8 weeks and 6 months following treatment. Pain response was determined by the international consensus on palliative radiotherapy and considered change in BPI and oral morphine equivalent dose (OMED). A planned interim analysis for futility was completed after 40 patients. Reirradiation with clinician choice regimens could be considered at ≥4 weeks following initial treatment for indeterminate pain response or pain progression. Forty patients were treated at 6 institutions between 2019 and 2022. Median age was 65 years with 40% women and 88% with an ECOG of 0-1. A complete response (CR) was defined as a BPI score of 0 with no concomitant increase in OMED. A partial response (PR) was defined as BPI reduction in 2 or more without analgesic increase, or an OMED reduction of 25% or more without an increase in pain. An indeterminate response (IR) was any response that is not captured by a CR, PR or pain progression. A CR was achieved in 48%, a PR in 38% of patients, an IR in 13% with 1 patient who refused participation. Pain response was achieved in 86% of patients. Seven patients (18%) requested reirradiation at ≥4 weeks. Median BPI at baseline and 4 weeks after RT for patients with CR, PR, and IR were 3.75 and 0, 4.00 and 1, and 5.25 and 4.75, respectively. Median change of BPI between baseline and 4 weeks after RT for all responders (CR and PR) was -3.25. The median PTV volume (cc) for patients with CR, PR and IR were 81, 140 and 226, respectively. Based on these results, the futility threshold was not met, and the recommendation by the DSMC is to continue the trial. In the first 40 patients who received 4 Gy palliation for painful bone lesions from multiple myeloma, there were 86% that had a pain response (48% CR, 38% PR). This low dose, response-adapted treatment, led to reirradiation in less than 20% of patients.