Faculty, Staff and Student Publications
Publication Date
1-1-2025
Journal
Frontiers in Immunology
Abstract
Background: Select patients with relapsed/refractory aggressive B cell lymphoma may benefit from bridging radiation (bRT) prior to anti-CD19-directed chimeric antigen receptor T cell therapy (CAR-T). Here, we examined patient and treatment factors associated with outcomes and patterns of failure after bRT and CAR-T.
Methods: We retrospectively reviewed adults with diffuse large B-cell lymphoma (DLBCL) who received bRT prior to axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel between 11/2017-4/2023. Clinical/treatment characteristics, response, and toxicity were extracted. Survival was modeled using Kaplan-Meier or Cox regression models for events distributed over time, or binary logistic regression for disease response. Fisher's Exact Test or Mann-Whitney U methods were used.
Results: Of 51 patients, 25.5% had bulky disease and 64.7% had Stage III/IV disease at the time of RT. Comprehensive bRT alone to all disease sites was delivered to 51% of patients, and 29.4% were additionally bridged with systemic therapy. Median follow-up was 10.3 months (95% CI: 7.7-16.4). Overall response rate (ORR) was 82.4% at 30 days post-CAR-T infusion. Median overall survival (OS) was 22.1 months (6.6-not reached) and the median progression-free survival (PFS) was 7.4 months (5.5-30). OS/PFS were 80% (66-99)/78% (64-87) at 1-year, and 59% (44-71)/54% (40-67) at 2-years, respectively. Comprehensive RT to all sites of disease correlated with improved PFS and OS, p ≤ 0.04. Additionally, ECOG ≥2 and Stage III/IV disease predicted poor OS (p ≤ 0.02). Disease bulk, IPI ≥3, and non-GCB histology were poor predictors for disease-specific survival (DSS), p< 0.05. The latter two, as well as bRT dose of ≤30 Gy predicted worse PFS (p< 0.05). Among patients with advanced stage disease, comprehensive bRT to all sites of disease (n=10) was not associated with improved OS and PFS compared to focal bRT (n=23), p>0.17. No difference was seen in bridging RT vs. chemoRT. Twenty-six patients developed relapse (50.9%), of which 46% was in-field. Risk of in-field relapse correlated with bulky disease (OR=7, 95% CI: 1.2-41, p=0.03) and lack of response at 30 day post-CAR-T evaluation (OR=16.8, 95% CI: 1.6-176, p=0.02), but not with bRT dose (p=0.27).
Conclusion: bRT and CART is a good treatment strategy for select patients with aggressive B cell lymphoma. Comprehensive bRT including all sites of disease is associated with improved outcomes.
Keywords
Humans, Lymphoma, Large B-Cell, Diffuse, Male, Female, Middle Aged, Aged, Immunotherapy, Adoptive, Retrospective Studies, Adult, Treatment Outcome, Receptors, Chimeric Antigen, Aged, 80 and over, Young Adult, CAR-T, chimeric antigen receptor, radiation therapy, bridging RT, DLBCL
DOI
10.3389/fimmu.2025.1517348
PMID
39958356
PMCID
PMC11825444
PubMedCentral® Posted Date
1-31-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
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