CD34

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Mantle cell lymphoma

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Lymphoma

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Nuclear medicine

Leukapheresis

International Journal of Radiation Oncology*Biology*Physics

Purpose/Objective(s)Anti-CD19-directed chimeric antigen receptor T-cell therapy (CART) is a new treatment option for patients with relapsed and/or refractory non-Hodgkin lymphoma (NHL). We reviewed the outcomes of patients receiving CART and the potential role of bridging radiation therapy (bRT) in reducing local recurrences.Materials/MethodsFollowing IRB approval, we retrospectively reviewed 120 patients with NHL who received CART between 2018 and 2020 at a multi-site single institution. Baseline clinical and treatment characteristics were compared between patients who received bRT (≤30 days prior to CART or after leukapheresis) and those who did not using chi-square and Fisher's exact tests. Overall-survival (OS) and progression-free survival (PFS) were defined from date of CART infusion and estimated by Kaplan-Meier curves. Response rate was based on the post-CART PET scan with the best attained response.ResultsOf 120 patients who received CART, 2 (1.7%) died soon after CART infusion from infection. Of the 118 remaining patients (88% diffuse large B-cell, 7.5% high-grade B-cell, 2.5% mantle cell, 2% primary mediastinal B-cell), 14 (12%) received bRT, while 104 (88%) did not (noRT). There were no significant differences in the baseline clinicopathological characteristics between the two groups. bRT was delivered with a median dose of 20 Gy (range 15-36) in 5 fractions (range: 3-24). No grade 2+ radiation-related toxicities were noted. Median time between end of bRT and the CART infusion was 19 days (range: 8-38). Rates of grade > 2 ICANS (21% vs 16%; P = .70) and CRS (7% vs 2%; P = .32) were not significantly different between bRT and noRT, respectively. Median follow-up was 7 months (range: 1-31). There were 42 (36%) deaths: 31 due to progression, 9 due to infection and 2 of unknown causes. The 6-month and 1-year OS were 67% and 67% for the bRT, and 76% and 63% for the noRT groups, respectively (P = .96). The median time to CART failure for the cohort was 78 days (range: 22-627). The 6-month and 1-year PFS were 47% and 47% for the bRT, and 47% and 42% for the noRT groups, respectively (P = .73). Median time to achieve the best response on PET scan was 30 days (range 22-382). Sixty patients (51%) achieved complete remission to CART, 7 (50%) in the bRT group and 53 (51%) in the noRT group, while 40 (34%) achieved partial remission, 5 (36%) in the bRT group and 35 (34%) in the noRT group (P = .97). For the entire cohort, pattern of failure analysis revealed that progression in pre-existing sites alone or in combination with new sites was the predominant site of failure in the bRT and noRT groups (86% and 88%, respectively). However, 71.4% of progressions in the bRT group occurred outside the RT field (n = 5), compared to 28.6% (n = 2) inside the RT field.ConclusionBridging RT prior to CAR T-cell infusion is well tolerated and appears to provide excellent in-field local control. Large prospective studies evaluating the value of integrating bRT with CAR T-cell therapy are needed. Anti-CD19-directed chimeric antigen receptor T-cell therapy (CART) is a new treatment option for patients with relapsed and/or refractory non-Hodgkin lymphoma (NHL). We reviewed the outcomes of patients receiving CART and the potential role of bridging radiation therapy (bRT) in reducing local recurrences. Following IRB approval, we retrospectively reviewed 120 patients with NHL who received CART between 2018 and 2020 at a multi-site single institution. Baseline clinical and treatment characteristics were compared between patients who received bRT (≤30 days prior to CART or after leukapheresis) and those who did not using chi-square and Fisher's exact tests. Overall-survival (OS) and progression-free survival (PFS) were defined from date of CART infusion and estimated by Kaplan-Meier curves. Response rate was based on the post-CART PET scan with the best attained response. Of 120 patients who received CART, 2 (1.7%) died soon after CART infusion from infection. Of the 118 remaining patients (88% diffuse large B-cell, 7.5% high-grade B-cell, 2.5% mantle cell, 2% primary mediastinal B-cell), 14 (12%) received bRT, while 104 (88%) did not (noRT). There were no significant differences in the baseline clinicopathological characteristics between the two groups. bRT was delivered with a median dose of 20 Gy (range 15-36) in 5 fractions (range: 3-24). No grade 2+ radiation-related toxicities were noted. Median time between end of bRT and the CART infusion was 19 days (range: 8-38). Rates of grade > 2 ICANS (21% vs 16%; P = .70) and CRS (7% vs 2%; P = .32) were not significantly different between bRT and noRT, respectively. Median follow-up was 7 months (range: 1-31). There were 42 (36%) deaths: 31 due to progression, 9 due to infection and 2 of unknown causes. The 6-month and 1-year OS were 67% and 67% for the bRT, and 76% and 63% for the noRT groups, respectively (P = .96). The median time to CART failure for the cohort was 78 days (range: 22-627). The 6-month and 1-year PFS were 47% and 47% for the bRT, and 47% and 42% for the noRT groups, respectively (P = .73). Median time to achieve the best response on PET scan was 30 days (range 22-382). Sixty patients (51%) achieved complete remission to CART, 7 (50%) in the bRT group and 53 (51%) in the noRT group, while 40 (34%) achieved partial remission, 5 (36%) in the bRT group and 35 (34%) in the noRT group (P = .97). For the entire cohort, pattern of failure analysis revealed that progression in pre-existing sites alone or in combination with new sites was the predominant site of failure in the bRT and noRT groups (86% and 88%, respectively). However, 71.4% of progressions in the bRT group occurred outside the RT field (n = 5), compared to 28.6% (n = 2) inside the RT field. Bridging RT prior to CAR T-cell infusion is well tolerated and appears to provide excellent in-field local control. Large prospective studies evaluating the value of integrating bRT with CAR T-cell therapy are needed.

Radiation Therapy as Bridging Treatment to CAR T Cell Therapy in Non-Hodgkin Lymphoma