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/METHODS: 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. RESULTS: 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. CONCLUSION: 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.
|Original language||English (US)|
|Journal||International journal of radiation oncology, biology, physics|
|State||Published - Nov 1 2021|
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging
- Cancer Research