Outcomes of Salvage Radiotherapy in Refractory or Relapsed High-Grade B-Cell Lymphoma Patients Treated with Commercial CAR T-Cell Therapy

Abstract

<h3>Purpose/Objective(s)</h3> We sought to describe our early experience of using salvage RT (SRT) in patients with high-grade B-cell lymphoma (HGBCL) who relapsed after CD19 targeted chimeric antigen receptor (CAR) T cell therapy. <h3>Materials/Methods</h3> A multi-institutional retrospective study was conducted for consecutive HGBCL patients who received axi-cel or tisa-cel CAR T-cell therapy between 2018 and 2021. Patients who relapsed following CAR T-cell therapy and received SRT were identified and analyzed using descriptive and statistical analysis. Only the first RT course was included for patients receiving >1 SRT course. Post-CAR T day 30 response, and post-CAR T best overall response, defined as the lowest disease burden measured at any time between post-CAR T-cell therapy and additional salvage therapies, were analyzed. Time to in-field progression was defined as the time from the start date of SRT until the time of in-field progression. <h3>Results</h3> 52 patients with HGBCL who received SRT post-CAR T were identified. The median age at diagnosis was 62 years (33-81 years). 32 patients received axi-cel, while 20 received tisa-cel. The median follow-up from the date of CAR T infusion was 12.5 months (range, 24 days-41.5 months) and the median follow-up from the start date of SRT was 5.7 months (range, 2 days-32.4 months). The post-CAR T day 30 and post-CAR T best response rates were 69.2% and 71.1%, respectively. The median time from CAR T-cell therapy infusion to SRT start was 4.0 months (range, 8 days-23.8 months). The median dose/fractionation were 35 Gy (range, 4-60.4 Gy) and 12.5 fractions (range, 1-33 fractions). Radiation details were incomplete for 13 patients who received SRT at outside institutions. The median time to in-field progression was 1.4 months (range, 20 days-2.3 months). Of the 46 evaluable patients, the complete response, partial response, stable disease, and in-field progression rates were 52% (n=24), 35% (n=16), 4% (n=2), and 9% (n=4), respectively. 2 of 12 patients (17%) with bulky disease (≥5 cm) had in-field recurrence versus 2 of 34 (6%), (p= 0.28) with non-bulky disease. The median OS from the start of CAR T-cell therapy was 19.6 months (95% CI: 12.7 months-not reached) and 12 months (95% CI: 7.27 months-not reached) from the start of SRT. <h3>Conclusion</h3> Our findings suggest that SRT may be a feasible and promising salvage therapeutic avenue that can provide local control post-CAR T failure. The trend toward a higher in-field progression in patients with bulky disease at relapse suggests that these patients may benefit from higher radiation doses.