Palliative radiotherapy (RT) is effective for multiple myeloma (MM) but may cause cytopenia. Bone marrow volume receiving 10Gy (BMV10Gy) has been associated with hematologic toxicity (HT) in cervical cancer, but no studies have investigated this in MM. We hypothesized that absolute BMV10Gy is associated with acute HT in MM patients receiving palliative RT.

This single-institution retrospective analysis evaluated 125 MM patients who received palliative RT between 2007-2023 and had ≥ 2 weeks of follow up laboratory data. Lab values were recorded pre-RT, post-RT, and at nadir within 90 days of completing RT. Clinical HT was defined as new transfusion/growth factor, admission for hematologic toxicity, and/or systemic therapy pause/discontinuation. BM was defined as bone volume within RT field. BMV5-40Gy (cc) was recorded for each treatment. Logistic regressions were performed with clinical HT as the primary endpoint.

105 (84%) patients received concurrent systemic therapy. Median BMV10Gy was 266cc (IQR 157-501cc). Median RT EqD2 was 26Gy (IQR 23-33Gy). On univariable analysis, BMV5Gy, BMV10Gy, and BMV15Gy were significantly associated with clinical HT (p=0.014, p=0.018, p=0.050, respectively) while RT EqD2 dose was not (p=0.997). On multivariable analysis, BMV10Gy was significantly associated with clinical HT (p=0.049) after adjusting for dose, number of lesions treated, lesion location (spine, pelvis, limb, soft tissue), and systemic therapy class. Disease course (number of prior systemic therapies) was significantly associated with clinical HT on univariable and multivariable analysis, with late relapsed/refractory patients (≥3 prior systemic therapies) having 9.6 higher odds of clinical HT compared to newly diagnosed patients (p<0.001).

To our knowledge, this is the first study to associate volume of irradiated BM with acute HT in MM. In addition to BM V5-15Gy, number of prior relapses and systemic therapy lines were significantly associated with HT. Disease history should be evaluated, and RT field volumes minimized for patients with poor bone marrow reserve (e.g., late relapsed/refractory disease).