Outcomes of salvage radiotherapy in relapsed/refractory large B-cell lymphoma patients following CAR T-cell therapy failure.

e19007 Background: Post-CAR T relapsed/refractory disease is a significant challenge in large B-cell lymphoma (LBCL) patients. Salvage radiotherapy (SRT) provides high local control and improves survival based on disease stage. We explored the long-term outcomes following SRT for post-CAR T failure. Methods: We conducted a retrospective study in a database of 352 consecutive LBCL patients who received CAR T-cell therapy following ≥2 prior therapies and subsequently received salvage therapies post-CAR T relapsed/refractory disease [RT alone, systemic therapy (ST) alone, or combined modality therapy (CMT)]. A separate analysis was conducted for patients who were treated with comprehensive versus focal RT. Results: 128 patients received salvage therapies (RT, 24 patients; CMT, 16 patients; ST, 88 patients). The median follow-up after CAR T-cell infusion was 14.2 months [interquartile range (IQR): 6.3-41.0 months], and the median follow-up after post-CAR T salvage therapy was 7.1 months (IQR: 3.0-24.0 months). The 2-year survival (OS) rate post-CAR T was 41%. Patients who had disease progression within 6 months after CAR-T infusion (n=93) had inferior OS compared with those who progressed later (n=35) (median OS of 7.3 vs. 23.7 months; p = 0.04). There was no significant difference in OS or progression-free survival (PFS) post-salvage therapy start date based on the class of salvage therapy. Analysis of patterns of failure revealed that the majority of patients (n=96, 75%) had a component of failure in previously involved sites pre-CAR T. A total of 103 sites were irradiated in 56 patients who received any salvage RT post-CAR T failure, including 26 CNS sites. The median dose/fractionation was 30 Gy (range, 4-50.4 Gy) and 10 fractions (range, 1-28 fractions). The 2-year in-field PFS was 71% for all irradiated sites and 74% for non-CNS sites. The median in-field PFS for the CNS sites was 26 months (95% CI: 10 months – not reached). Seventeen sites experienced local recurrence with a median time to in-field progression of 3.5 months (IQR: 2.4-9.8 months). There was improved in-field PFS for non-CNS sites that received high-dose RT (BED 10 ≥ 39 Gy) as compared to sites that received low-dose RT (BED 10 <39 Gy) (median in-field PFS: not reached vs. 11.4 months, p= 0.03 ). The 2-year OS and PFS rates for patients who received comprehensive RT (n=31) vs. focal RT (n=25) were 57% vs. 10% ( p<0.0001 ), and 37% vs. 5% ( p=0.0008 ), respectively. Conclusions: Salvage RT is associated with excellent in-field control, but it declines over time with >70% in-field local control at 2 years for systemic disease. There was no difference in outcomes between SRT, ST, or CMT. Comprehensive RT is associated with superior survival outcomes compared to those receiving focal RT when disease burden allows. Higher doses (BED 10 ≥ 39 Gy) of RT were associated with improved in-field PFS in systemic disease.