Radiation therapy safe before CAR T-cell infusion for advanced multiple myeloma
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Localized radiation therapy appeared safe before treatment with chimeric antigen receptor T cells for relapsed or refractory multiple myeloma, according to study results presented at the virtual ASTRO Annual Meeting.
Results of the retrospective study showed radiation therapy before CAR T-cell therapy did not increase treatment-related major adverse events, and researchers observed no negative effects on treatment efficacy.
CAR T cells can take up to 4 weeks to manufacture, during which time a portion of patients waiting for infusion experience disease progression.
Additional systemic therapy would be unnecessary at this point because these patients have progressed after multiple previous lines of therapy, according to Shwetha H. Manjunath, MD, resident in the department of radiation oncology at University of Pennsylvania.
However, radiation therapy can be “quite effective at dealing with localized issues,” such as pain related to the development of a specific lesion, Manjunath said.
“What is unknown is whether radiation during this time would negatively affect one’s ability to respond to CAR T cells or if it would increase levels of toxicity,” she told Healio.
Manjunath and colleagues retrospectively analyzed data from a phase 1 study of 25 patients conducted at University of Pennsylvania to evaluate B-cell maturation antigen (BCMA)-directed CAR T-cell therapy among patients with relapsed or refractory multiple myeloma.
The study included three cohorts of patients assigned the following treatments: 1-5 × 108 BCMA-CAR T cells (n = 9); cyclophosphamide dosed at 1.5 g/m2 plus 1-5 × 107 BCMA-CAR T cells (n = 5); or cyclophosphamide dosed at 1.5 g/m2 plus 1-5 × 108 BCMA-CAR T cells (n = 11).
The investigators collected data on radiation therapy, treatment responses, toxicities and CAR T-cell manufacturing. They graded toxicities using Common Terminology Criteria for Adverse Events version 4.0. They used University of Pennsylvania’s institutional grading system to grade cytokine release syndrome (CRS), and they used International Myeloma Working Group criteria to assess responses to therapy.
Thirteen patients did not receive radiation therapy within 1 year of CAR T-cell infusion (group 1). Eight patients received radiation therapy within 1 year of infusion (group 2), with median time from radiation therapy to apheresis of 88.5 days (range, 15-295). Four patients received bridging radiation therapy (group 3), with median time of 17 days (range, 14-22) from apheresis to radiation therapy and 34 days (range, 21-42) from bridging therapy to CAR T-cell infusion.
Results showed group 3 had lower rates of grade 4 hematologic toxicities than groups 1 and 2 (25% vs. 61.5% and 62.5%), and no grade 3 or greater infections or liver-related toxicities.
Group 1 had the lowest rate of neurotoxicity (7.7%), compared with a 25% rate in groups 2 and 3. Researchers reported two cases (25%) of grade 4 neurotoxicity in group 2.
The groups had comparable rates of grade 2 CRS, whereas group 1 had a slightly higher rate of grade 3 CRS than groups 2 and 3 (38.5% vs. 25% and 25%). Only one patient, in group 2, experienced grade 4 CRS.
The efficacy analysis showed radiation therapy before CAR T-cell infusion did not have a negative effect on response rates.
“Localized radiation therapy is safe and doesn’t appear to worsen CRS or neurotoxicity when given prior to CAR T-cell therapy,” Manjunath told Healio. “There also appears to be comparable CAR T-cell efficacy with those who did not receive radiation.”
Although the results are encouraging, no definitive conclusions can be made from a retrospective study of this size, she added.
One area of future study may be whether radiation therapy can enhance the efficacy of CAR T cells, Manjunath said.
Higher doses of CAR T cells have been shown to produce more effective responses, she said. Two patients in her study who received the lowest dose of CAR T cells plus radiation showed an objective response to therapy compared with none of the patients who received low-dose CAR T cells only.
“It wasn’t a good response. It was a minimal response, but it was at least some form of objective response,” Manjunath said. “These results are very hypothesis-generating.”
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