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Bridging Radiation Therapy Plus Immunotherapy for Resistant Multiple Myeloma

By: Joseph Fanelli
Posted: Thursday, December 9, 2021

For patients with relapsed or refractory multiple myeloma, bridging radiation with B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T cells appears to be a safe and feasible treatment option, according to findings presented in Clinical Cancer Research. Ima Paydar, MD, of the Abramson Cancer Center at the University of Pennsylvania, Philadelphia, and colleagues found that bridging radiation with anti-BCMA CART T-cell therapy did not worsen the rates of severe cytokine-release syndrome, neurotoxicity, or hematologic toxicity.

“The time to peak expansion, the activation of CART-BCMA cells, or the frequency of CART-BCMA cells within CD3+, CD4+, and CD8+ populations in vivo at peak expansion appeared similar between those who did and did not receive bridging radiation therapy,” the authors concluded.

In this phase I trial, the authors enlisted 25 patients with relapsed or refractory multiple myeloma and treated each with two doses of anti-BCMA CART T-cell therapy with or without cyclophosphamide. Of the group, 13 patients did not receive radiation less than 1 year before CAR T-cell infusion, 8 patients did receive radiation less than 1 year before CAR T-cell infusion, and 4 patients received bridging radiation therapy with a median dose of 22 Gy.

The authors found that patients who received bridging radiation therapy demonstrated “qualitatively” lower rates of grade 4 hematologic toxicities (25%), compared with those who did not receive radiation (61.5%) and those who did (62.5%). Additionally, grade 3 or 4 neurotoxicities occurred in 7.7% of patients who did not receive radiation, and 25% each in those who received radiation and those who received bridging radiation therapy.

In patients not given radiation treatment, 54% had a partial response or better to treatment, compared with 38% of those receiving radiation and 50% in those treated with bridging radiation therapy. Treatment with radiation that was administered less than 1 year and less than 100 days before apheresis was linked to lower in vitro proliferation during manufacturing, but in vivo anti-BCMA CART T-cell therapy expansion was similar across all subgroups, the authors said.

Disclosure: For full disclosure of the study authors, visit aacrjournals.org.



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