CAR T-Cell Therapy Reduces Fracture Risk in Patients with Multiple Myeloma

New study findings indicate that chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) multiple myeloma (MM) is associated with lower fracture risk, which the researchers attribute to lesion resolution. These data will be presented at the AAOS 2025 Annual Meeting.

Patients with R/R MM often have a high burden of skeletal disease and may be at risk for pathologic fractures. CAR T-cell therapy is a relatively new treatment modality that genetically engineers T cells to activate the immune system so that it can recognize and destroy certain types of cancer. Little is known about this immunotherapy’s effects on fracture risk.

“This is the only study to date that examines this specific patient population undergoing this specific treatment. We found that following CAR T-cell infusion, there was a significant reduction in fracture risk, suggesting that CAR T-cell therapy could be valuable not only in managing MM but also managing the risk of pathologic fracture that comes with this malignancy,” said author Alexander Lazarides, MD, orthopaedic oncology surgeon at Moffitt Cancer Center in Tampa, Florida.

The researchers retrospectively reviewed 139 consecutive patients with MM who received CAR T-cell therapy and also had a positron emission tomography (PET)-CT scan prior to CAR T-cell infusion and at least one PET-CT scan 90 days after treatment. The patients’ mean age was 64.4 years, and 58 (41.7 percent) patients were female. Minimum follow-up time for inclusion was 3 months, and mean follow-up for surviving patients was 9.5 months (range, 3–28 months). Of the 139 patients, 71 (51.4 percent) had a discrete long-bone lesion.

Prior to CAR T-cell therapy, 37 patients (27.8 percent) were considered “at risk” for fracture, as determined by a modified Mirels’ Classification. After CAR T-cell therapy, at latest follow-up, only three patients (2.5 percent) were considered at risk (P = 0.004). The improvement in Mirels scoring was mostly attributable to resolution of bone lesions and improvements in pain.

The researchers also assessed changes in lesion avidity, per PET-CT standardized uptake value (SUV) units. Prior to CAR T-cell infusion, the mean PET-CT SUV was significantly different between at-risk patients and those at low risk (8.2 versus 4.6, respectively, P = 0.03). After therapy, there was no significant difference (5.7 versus 4.0, respectively, P = 0.43). In the entire cohort, two fractures occurred, and 33 patients died at a mean 6.6 months. The authors found no association between pre-therapy fracture risk and survival.

“MM has historically been a radiation-responsive entity. Nonetheless, radiation affects both normal bone and the tumor, and often there is still benefit to consider prophylactic stabilization,” Dr. Lazarides said. However, with CAR T-cell therapy, “Anecdotally, we have seen MM lesions disappear in a matter of weeks, indicating that these patients may not require prophylactic fixation. To see such a rapid resolution of these bone lesions and the associated healing of the bone is truly remarkable.”

The authors cautioned that the results do not supplant the need for strong clinical judgment and a multidisciplinary approach to care. They plan future research comparing patients receiving standard treatment with those receiving CAR T-cell therapy to better understand the extent to which CAR T-cell therapy may reduce risk.

“This study highlights the importance of keeping up to date with modern approaches to the treatment of metastatic bone disease. As treatments advance, patients are living longer with their disease, and increasingly there is a need to approach metastatic bone disease in a multidisciplinary manner, taking into account histology and lesion features, local and systemic treatment options, and overall patient comorbidities. There is nowhere that this is embodied more than with the increasing utilization of CAR T-cell therapy,” Dr. Lazarides said.

Paper 055 will be presented during VIPER: Musculoskeletal Oncology I Papers, 11 a.m. on Monday in Room 8.

Dr. Lazarides’ coauthors of “Evaluating the Influence of Chimeric Antigen Receptor T-Cell Therapy on Fracture Risk of Patients with Multiple Myeloma” are Thien Huong N. Huynh, BS; Bryan Clampitt, BS; Chloe Min Chose, BS; Matthew Daniel Nester; Davis Kuruvilla, BS; David Joyce, MD, FAAOS; Odion T. Binitie, MD, FAAOS; and Ciara Louise Freeman, MD, PhD.

Keightley Amen, BA, ELS, is a freelance writer for AAOS Now.