Comprehensive Salvage Radiotherapy for Limited Relapsed B-Cell Non-Hodgkin Lymphoma Following CD19 Chimeric Antigen Receptor T-Cell Therapy

Abstract

<h3>Purpose/Objective(s)</h3> Significant relapse rates following CD19 Chimeric Antigen Receptor T-Cell Therapy (CART) for relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (NHL) remain a challenge. This study aims to better define the role of salvage radiotherapy (SRT) after CART. <h3>Materials/Methods</h3> We retrospectively reviewed 48 patients with r/r aggressive B-cell NHL who received SRT following CART from 2018 to 2021. SRT local control rate (LC) - calculated based on the total number of irradiated sites, freedom from subsequent progression (FFSP), freedom from subsequent event (FFSE) – accounting for subsequent progressions and salvage therapies, and overall survival (OS) were defined from SRT start date. In-field recurrence was defined as disease relapse occurring within the radiation planning target volume. SRT was defined as comprehensive (compSRT) – treated all sites of active disease – or focal (focSRT). Limited disease was defined as disease amenable to comprehensive RT, either as localized (encompassable in one RT field) or oligo-diffuse (≤4 sites). Kaplan-Meier plots and Cox regression modeling were used to estimate the desired output. <h3>Results</h3> Median age of the cohort at time of CART infusion was 58 (range 19-73) years, and median time from CART infusion to SRT was 103 (range: 23-842) days. The median equivalent 2 Gy dose (EQD2) was 37.4 Gy (range 4-52 Gy) for compSRT and 24.2 Gy (range 4.7-48.8) for focSRT. The most common regimens were 36 Gy in 12 fractions in compSRT and 20 Gy in 5 fractions in focSRT. A total of 65 sites treated in 37 patients had adequate imaging follow-up after SRT. Of the irradiated sites, 21 lesions (32%) in 16 patients experienced in-field recurrence, translating to 1-year LC of 62%. No in-field recurrence occurred beyond 210 days. On univariate analysis, tumor size, SUVmax, and LDH >2x upper limit (UL) at the time of SRT were significantly associated with increased risk of in-field recurrence. On the multivariate analysis, LDH >2x UL (OR 6.5, CI: 1.8-24.3; p=0.005) and SUVmax (OR 1.06, CI: 1.002-1.12; p=0.044) retained significant association with in-field recurrence. There were 37 patients with limited disease and 11 with extensive disease and the 1-year OS was 39% and 0% (p<0.001), respectively. Among those with limited disease, 26 received compSRT and 11 received focSRT. At a median follow-up period of 20 months, patients with limited disease who received compSRT had significantly higher 1-year FFSP (31% vs. 0%; p<0.001), 1-year FFSE (19% vs. 0%; p=0.01), and 1-year OS (51% vs. 12%; p=0.028) compared to focSRT. <h3>Conclusion</h3> Post-CART compSRT for r/r B-cell NHL is a reasonable salvage intervention for patients with limited relapsed disease and is associated with better FFSP, FFSE and OS compared to focSRT. Patients who have elevated LDH >2 x UL and high SUVmax prior to SRT are likely at the highest risk of in-field recurrence and may benefit from escalation of therapy.