Influence of Chimeric Antigen Receptor T-Cell Therapy on Fracture Risk of Patients With Multiple Myeloma

Patients with relapsed or refractory multiple myeloma (MM) often have a high burden of skeletal disease and may be at risk for pathologic fracture. These patients may be eligible for chimeric antigen receptor T-cell (CAR-T) therapy. However, little is known about the effect of CAR-T therapy on a patient's fracture risk. The purpose of this study is to evaluate this effect. A consecutive cohort of MM patients undergoing treatment with CAR-T therapy were reviewed retrospectively. Patients were required to have a PET-CT before CAR-T infusion and at least one PET-CT surveillance imaging 90 days following treatment. The minimum follow-up for surviving patients was set at 3 months. The primary outcome measure was fracture risk as characterized by a modified Mirels criteria. The secondary outcome measure was change in lesion avidity, measured as standardized uptake value units, on PET-CT. Survival was investigated by Kaplan-Meier method. We identified 139 patients who underwent CAR-T for MM. Overall, 71 patients (51.4%) had a discrete long bone lesion, and 37 patients (27.8%) were characterized as being "at risk" for fracture before infusion. After CAR-T, three patients (2.5%) were identified as being at risk (P = 0.004). The mean PET-CT standardized uptake value between at risk patients and those at low risk was markedly different before infusion (9.18 vs. 6.75, P = 0.03). For these same patients, no difference was identified after CAR-T therapy (5.75 vs. 4.67, P = 0.26). Three fractures occurred in the posttransfusion period; 33 patients (23.7%) died of disease after CAR-T therapy at a mean of 6.6 months. Following CAR-T infusion, a notable reduction was observed in fracture risk, suggesting that CAR-T could be valuable not only in managing MM but also in managing the risk of pathologic fracture that comes with this malignancy.