PURPOSE: Palliative radiation therapy (RT) is effective for multiple myeloma (MM) but may cause cytopenia. Bone marrow volume receiving 10 Gy (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. MATERIALS AND METHODS: This single institution retrospective analysis evaluated 125 MM patients who received palliative RT between 2007 and 2023 and had ≥2 weeks of follow-up laboratory data. Laboratory 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 HT, and/or systemic therapy pause/discontinuation. BM was defined as a bone volume within the RT field. BMV5-40Gy (cubic centimeter [cm RESULTS: Around 105 (84%) patients received concurrent systemic therapy. Median BMV10Gy was 266 cm CONCLUSIONS: To our knowledge, this is the first study to associate the volume of irradiated BM with acute HT in MM. In addition to BMV5-15Gy, number of prior relapses and systemic therapy lines were significantly associated with HT. Disease history should be evaluated, and RT field volumes were minimized for patients with poor bone marrow reserve (eg, late relapsed/refractory disease).