Irradiated Bone Marrow Volume is Associated With Hematologic Toxicity in Patients With Multiple Myeloma

Int J Radiat Oncol Biol Phys. 2024 Oct 28:S0360-3016(24)03509-0. doi: 10.1016/j.ijrobp.2024.10.017. Online ahead of print.

Abstract

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 [cm3]) was recorded for each treatment. Logistic regressions were performed with clinical HT as the primary endpoint.

Results: Around 105 (84%) patients received concurrent systemic therapy. Median BMV10Gy was 266 cm3 (IQR, 157-501 cm3). Median RT equivalent dose in 2 Gy fractions was 26 Gy (IQR, 23-33 Gy). On univariable analysis, BMV5Gy, BMV10Gy, and BMV15Gy were significantly associated with clinical HT (P = .014, P = .018, P = .050, respectively), while RT equivalent dose in 2 Gy fractions dose was not (P = .997). On multivariable analysis, BMV10Gy was significantly associated with clinical HT (P = .049) after adjusting for dose, number of lesions treated, lesion location (spine, pelvis, limb, and 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 < .001).

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).