ASTRO 2026: Where Does Multiple Myeloma Relapse Occur After BCMA CAR T-Cell Therapy?
By: Lisa Astor
Posted: Friday, October 23, 2026
Multiple myeloma that recurs after B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy tends to reappear outside the bone marrow, and the amount of extramedullary or paramedullary disease present before infusion strongly predicts worse outcomes, according to findings presented at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract 207).
Although CAR T-cell therapy can produce lasting remissions in relapsed or refractory multiple myeloma, most patients eventually experience disease progression, and where that progression occurs has not been thoroughly mapped. Investigators led by Alexandra Dreyfuss, MD, MS, of the University of Miami Sylvester Comprehensive Cancer Center, along with colleagues at Memorial Sloan Kettering Cancer Center, set out to describe patterns of disease progression and identify high-risk sites that might benefit from radiation therapy.
The team reviewed 102 patients treated with ciltacabtagene autoleucel between 2018 and 2024 who underwent serial FDG PET/CT imaging. Scans were assessed at four points: before apheresis, before lymphodepleting chemotherapy, on day 30 after CAR infusion, and at first progression. Individual lesions were tracked over time, with metabolic response and progression graded by standardized uptake values using Lugano criteria, since multiple myeloma lacks an agreed imaging standard.
At a median follow-up of 19 months, the 24-month progression-free survival rate was 48% (95% confidence interval [CI] = 37%–61%) and the overall survival rate was 74% (95% CI = 64%–85%). Most relapses were both biochemical and radiologic (63%), and radiologic progression often involved a mix of old and new sites. Extramedullary disease was present in 26% of patients before CAR T-cell therapy and rose to 47% at progression, while paramedullary disease climbed from 12% to 25%. Bone-only disease fell from 62% to 28%.
Extramedullary and paramedullary disease measured before lymphodepletion independently predicted shorter progression-free survival (paramedullary hazard ratio [HR] = 20.4, 95% CI = 7.2–58.0; extramedullary HR = 7.1, 95% CI = 2.9–17.1) and shorter overall survival. Lesion by lesion, 41% of extramedullary and 31% of paramedullary sites progressed vs 11% of bone lesions. At day 30, only 2% of lesions in complete metabolic response later progressed, compared with 27% of partial responders and 40% of those with stable disease.
“These findings suggest rational, lesion-level criteria to integrate bridging or consolidative radiotherapy to potentially improve CAR T[-cell therapy] outcomes in relapsed/refractory multiple myeloma,” the study authors concluded.
