Consolidative Radiotherapy for Residual PET-Avid Disease on Day +30 Post CAR T-Cell Therapy in Non-Hodgkin Lymphoma

Abstract

Up to30% of non-Hodgkin lymphoma (NHL) patients achieve a partial response (PR) to anti-CD19 Chimeric Antigen Receptor T-cell Therapy (CART) on day +30. Most PR patients relapse and only 30% achieve spontaneous complete response (CR) without additional therapies. This study is the first to report on the role of consolidative radiotherapy (cRT) for PR PET-avid disease on day +30 post-CART in NHL. Aretrospective review across 3 institutions from 2018 to 2022 identified 60 patients with B-cell NHL who received CART and achieved PR (Deauville 4-5) with <5 PET-avid disease sites on day +30. Progression-free survival (PFS) was defined from CART infusion to any disease progression. Overall survival (OS) was defined from CART infusion to death. Local relapse-free survival (LRFS), calculated based on the total number of PR sites, was defined from CART infusion to local relapse (LR) in the PR site identified on day +30. cRT was defined as comprehensive (compRT) - treated all PR PET-avid sites - or focal (focRT). Followingday +30 PET scan, 45 PR patients were observed and 15 received cRT. Only one patient received consolidative systemic therapy and belonged to the cRT group. Prior to CART, bridging RT was given to 13 patients (9 in observation group and 4 in cRT group). There were no significant differences in the pre-CART and day +30 baseline characteristics, including the median size and SUVmax of the PR sites, between the two groups. However, the median number of PR sites on day +30 was higher in the cRT group (2 [range 1-3] vs 1 [range 1-3], p = 0.003). The median equivalent 2 Gy dose was 39.1 (Interquartile range 36.8-41) Gy, and the most common cRT regimen was 37.5 Gy in 15 fractions. The median follow-up was 21 months. Among the observed patients, 15 (33%) achieved spontaneous CR, and 27 (60%) experienced disease progression with all relapses involving the initial PR sites. Among patients who received cRT, 10 (67%) achieved CR, and 3 (20%) had disease progression with no relapses in the radiated PR sites. None of the 10 cRT patients achieving CR relapsed or required subsequent therapies. The 2-year PFS was 80% and 37% (p = 0.012) and the 2-year OS was 78% and 43% (p = 0.12) in the cRT and observation groups, respectively. Patients consolidated with compRT (n = 12) had superior 2-year PFS (92% vs 37%, p = 0.003) and 2-year OS (86% vs 43%, p = 0.048) compared to observed or focRT patients (n = 48). There were no grade 3+ RT-related toxicities. A total of 90 PR sites were identified; 64 were observed and 26 received cRT. Fourteen (22%) observed PR sites achieved spontaneous sustained CR and 42 (66%) experienced LR. Twenty-four (92%) PR sites consolidated with cRT achieved sustained CR and none experienced LR. The 2-year LRFS was 100% in the cRT sites and 31% in the observed sites (p<0.001). NHL patients who achieve PR by PET to CART are at high risk of local progression. cRT for residual PET-avid disease on day +30 post-CART appears to alter the pattern of relapse and improve LRFS and PFS.