3365 - Bridging Radiotherapy prior to Brexucabtagene Autoleucel for Relapsed/Refractory Mantle Cell Lymphoma

A. Fetooh¹, A. Lionel¹, P. Fang², C. C. Nze¹, S. Ahmed¹, J. Westin¹, C. Flowers¹, C. C. Pinnix², B. Dabaja², J. R. Gunther², S. S. Neelapu¹, M. L. Wang¹, P. Jain¹, and S. Y. Wu²; ¹Department of Lymphoma-Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, ²Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

Purpose/Objective(s): Brexucabtagene autoleucel (BA) is a CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy approved in the treatment of relapsed/refractory (r/r) mantle cell lymphoma (MCL). We aimed to characterize the use of bridging radiation (bRT) in this setting and identify potential benefits to incorporating RT into bridging regimens. Materials/

Methods: We conducted a single institution retrospective review of 17 patients (pts) who underwent apheresis between 3/2021 and 12/2023 for standard of care BA and received bRT. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were assessed using the American Society for Transplantation and Cellular Therapy criteria. Progression-free survival (PFS) was measured from BA infusion to progression or death. Overall response rate (ORR) included complete and partial response (CR/PR) using Lugano criteria.

Results: Thirteen (76%) pts were male. Sixteen (94%) had stage 4 disease at diagnosis. The median time from diagnosis to CAR-T was 20 months (interquartile range (IQR) 11-33), with a median of 3 lines of therapy prior to apheresis (IQR 2-4). Pathologic features included blastoid/pleomorphic histology (12 pts, 71%), Ki67 >50% (13, 76%), and TP53 mutations (13, 76%). Ten pts (59%) had progression within 24 months of first-line therapy.

The most common bST, combined with bRT, was rituximab-hypercytoxan-dexamethasone (7 pts, 41%). Three pts (18%) received bRT alone. All patients received bRT to symptomatic sites of disease, with pain most common (14 pts, 82%). The median dose was 4 Gy (IQR 4-11 Gy) in 2 fractions (IQR 2-5). RT was comprehensive (cRT), targeting all sites of known disease, in 3 pts (18%).

The ORR to bridging therapy was 41% (7/17); 10 pts had PD on pre-CAR T imaging. The ORR in the RT field was 59% (10/17), however the time from RT to PET/CT was short (median 20 days). The median time from RT end to BA infusion was 26 days (IQR 12-43). Grade 3+ (G3+) CRS was noted in 1 pt (6%) and G3+ ICANS was noted in 6 pts (35%).

On post-BA day 30 PET/CT, 12 pts (71%) experienced a CR, with 3 PRs (18%). At a median follow-up of 14 months post BA (IQR 4-29 months), the best response was a CR in 14 pts (82%). Four pts (24%) experienced progression.

cRT was associated with lower rates of CRS (1/3 vs. 13/14 in those who did not receive cRT, p = 0.014) and ICANS (0/3 vs. 10/14, p = 0.023); bulky disease and response to bridging therapy were not. cRT was associated with less frequent steroid (0/3 vs. 10/14, p = 0.023) and tocilizumab (0/3 vs. 9/14, p = 0.043) use post-BA. The median PFS was 14 months (IQR 3-29), and was not significantly longer for those who received cRT (median 28 vs. 10 months, p = 0.13)
Conclusion: In a high-risk group of patients with r/r MCL, bridging therapy with RT to a modest dose prior to CAR-T cell therapy is associated with promising CR rates and PFS, and may decrease treatment-related toxicity. Further prospective investigation is warranted.