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October 1, 2026 — A lesion-level PET/CT analysis of 102 patients with relapsed/refractory multiple myeloma (RRMM) finds that extramedullary or paramedullary disease present before CAR T-cell infusion is independently linked to markedly worse progression-free and overall survival. The study, presented at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting in Boston, also shows that relapse patterns tend to shift away from bone-only involvement toward these soft-tissue compartments, making them plausible targets for bridging or consolidative radiation.
Multiple myeloma remains difficult to cure once patients relapse through several lines of treatment. BCMA-directed CAR T-cell therapies such as ciltacabtagene autoleucel (Carvykti) have changed expectations in RRMM, sometimes producing deep remissions even in heavily pretreated patients. But post-CAR T relapses still occur, and the anatomical routes those relapses take have been poorly mapped.
This study helps address that gap. By tracking individual lesions on PET/CT scans, the research team led by Alexandra Dreyfuss, MD, MS, of the University of Miami Sylvester Comprehensive Cancer Center, quantified how often disease progression emerges outside the bone marrow and how strongly that pattern predicts outcome.
The findings were striking. Patients with extramedullary disease at baseline had a 7.1-fold higher risk of progression or death. Those with paramedullary disease faced a 20.4-fold higher risk. Overall survival was also substantially worse, with hazard ratios of 3.9 and 5.4, respectively.
These associations held in adjusted analysis, suggesting that non-bone disease is not just a marker of burden but an independent driver of poor outcomes. That is clinically important because extramedullary and paramedullary lesions are often difficult to reach with standard systemic therapy and may require local control strategies such as radiation.
In an interview with CancerNetwork®, Dreyfuss said that the biggest unmet need is prospective research on radiation in multiple myeloma. Only a handful of prospective studies have been completed on any radiation-related question in this disease, she noted.
One reason for the scarcity is that dose selection for myeloma remains unsettled. In practice, radiation doses range widely, from some of the lowest doses used in oncology to some of the highest reserved for radioresistant tumor types. That lack of standardization makes it difficult to design trials and to compare outcomes across institutions.
Dreyfuss pointed to the CAR T-cell and bispecific antibody spaces as the most logical places to begin prospective work. These therapies have high response rates and are increasingly used, but radiation has not yet been systematically tested as an adjunct in either platform.
She outlined two possible trial concepts: using radiation as a bridge before CAR T-cell infusion, and delivering radiation in the early post-CAR T period to consolidate response. In the bispecific antibody setting, radiation may also be used to target sites with the highest risk of failure.
“There’s definitely an opportunity in those 2 populations to translate what we’re seeing on a retrospective basis into prospective work,” she said.
For radiation oncologists and hematologists, this study offers a more precise way to think about relapse after CAR T-cell therapy. Baseline extramedullary or paramedullary disease may identify patients who need aggressive local therapy as part of their sequencing strategy. The later shift toward non-bone relapse sites supports the idea that radiation should no longer be viewed only as a palliative tool in myeloma.
Still, Dreyfuss cautioned that routine integration of radiation into CAR T or bispecific treatment plans will require prospective confirmation. The results come from a single-institution retrospective cohort, and the hazard ratios, while dramatic, need external validation in larger, multi-institutional datasets.
The study was presented as Abstract 207 at the 2026 ASTRO Annual Meeting, held September 26–30, 2026, in Boston.
Dreyfuss A, Yahalom J, Nemorovsky D, et al. Patterns of progression after BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma: a lesion-level PET/CT analysis. Presented at: 2026 ASTRO Annual Meeting; September 26-30, 2026; Boston, MA. Abstract 207.
