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Induction radiation therapy before CAR-T reduces treatment-related toxicities
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Patients who received radiation therapy before chimeric antigen receptor T-cell therapy for relapsed or refractory non-Hodgkin lymphoma were less likely to have severe treatment-related toxicities, according to results of a study presented at the American Society of Radiation Oncology Annual Meeting.
None of the patients who received induction radiation therapy less than 30 days before CAR T-cell infusion experienced high-grade (3/4) cytokine release syndrome or neurotoxicity — two of the common treatment-related toxicities associated with CAR T-cell therapy.
“Patients with relapsed/refractory non-Hodgkin lymphoma may have severe, chemorefractory disease that must be kept at bay during the several weeks between leukapheresis and ultimate CAR-T infusion,” Michael J. LaRiviere, MD, study co-author and a radiation oncology resident physician at the University of Pennsylvania Perelman School of Medicine, told Cell Therapy Next. “Because lymphoma is sensitive to radiotherapy, we sought to understand whether involved site radiation, delivered prior to CAR-T infusion, would be a feasible and safe bridging therapy approach,” he added.
Researchers from the University of Pennsylvania evaluated medical records of 31 patients who underwent CAR T-cell therapy at its medical center for relapsed or refractory non-Hodgkin lymphoma between August 2018 and February 2019. Eighteen patients in the study group received axicabtagene ciloleucel (Yescarta, Kite/Gilead), while 13 patients received tisagenlecleucel (Kymriah, Novartis).
The patients were then divided into three groups based on exposure to radiation therapy: one group received bridging radiation therapy, done during the 30 days after apheresis for CAR T-cell therapy but before CAR T-cell infusion (n = 5); the second group had radiation therapy at some point before (30 days; median 454 days; range, 45-2,048 days) CAR T-cell infusion but not as a bridging therapy (n = 7); and the third group did not have any radiation therapy (n = 19).
The investigators evaluated treatment-related cytokine release syndrome (CRS) and neurotoxicity according to the Penn scoring system.
Nearly all patients (17 of 18) who received axicabtagene ciloleucel underwent lymphodepletion with fludarabine and cyclophosphamide before CAR T-cell infusion; the remaining patient received bendamustine. Twelve of 13 patients who received tisagenlecleucel underwent lymphodepletion with bendamustine before CAR T-cell infusion; the remaining patient received fludarabine and cyclophosphamide.
The median induction (<30 days before infusion) radiation therapy dose was 3,750 cGy (range 2,000-4,500 cGy in 220-400 cGy fractions).
No patient who had induction radiation therapy experienced grade 3 or higher CRS, with two of five patients having grade 2 CRS and three patients with no CRS. Among patients who had radiation therapy greater than 30 days before CAR T-cell infusion, one patient had grade 3 CRS, three patients had grade 2 CRS, one patient had grade 1 CRS, and two patients had no recorded CRS.
For patients who had no radiation therapy before CAR T-cell infusion, five patients had grade 3 CRS, five had grade 2 CRS, and one patient had grade 1 CRS; seven of the 19 patients with no previous radiation therapy had no evidence of CRS. One patient in the group without previous radiation therapy had grade 4 neurotoxicity that had not resolved as of 153-day follow-up.
Patients who received axicabtagene ciloleucel had a significantly higher incidence of CRS (P < .001) and neurotoxicity (P < .05).
At a median follow up of 139 days (range, 10-261), two of 31 patients died, including one patient who received previous radiation therapy and one patient who did not. Fourteen of 31 patients had disease progression, including two patients who had prior previous radiation therapy, 10 patients with no previous radiation therapy and two patients who had induction radiation therapy.
“No high-grade cytokine release syndrome or neurotoxicity — they key severe toxicities of CAR-T therapy — was seen in patients who received radiation within 30 days of CAR-T infusion. There was no detected difference in overall or progression-free survival. These results suggest that this approach may safely and effectively be used to clinically stabilize patients while they await CAR-T infusion,” LaRiviere told Cell Therapy Next.
“Prior to widespread adoption, this approach should be tested in a prospective clinical trial, which we currently have in development,” he added. – by Drew Amorosi
Reference: LaRiviere MJ, et al. Abstract 135. Presented at: ASTRO Annual Meeting; September 15-19, 2019; Chicago.
For more information:
Michael J. LaRiviere, MD, can be reached at michael.lariviere@uphs.upenn.edu.
Disclosures: LaRiviere reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
Back to TopRichard Bakst, MD, Associate professor of radiation oncology
The study by LaRiviere and colleagues demonstrates that radiation therapy can be safely used in conjunction with CAR T-cell infusion. Patients awaiting treatment with CAR T cells often need a bridging therapy until their modified cells are ready and returned from the manufacturing facility. This bridging therapy oftentimes includes chemotherapy. Radiation offers a potential alternative therapy if localized disease occurs.
The results of the study by LaRiviere and colleagues provides further evidence that combined modality therapy is essential for the effective treatment of lymphomas. Radiation therapy should be considered as a bridge to any other systemic therapy used for the treatment of lymphoma.
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