Favorable Outcomes with Bridging Radiation Therapy Prior to Anti-CD19 Chimeric Antigen Receptor T-Cell CART in B Cell Lymphoma, a Report from Saudi Arabia

Objective:

To analyze the outcomes of B cell Lymphoma patients who received bridging Radiation therapy (XRT) prior to anti-CD19 CART axicabtagene ciloleucel (Axi-cel).

Methods:

Retrospective review of patients with relapsed/refractory B cell lymphoma who received anti-CD19 CART axicabtagene ciloleucel (Axi-cel), since its launch in King Faisal specialist Hospital and Research Center from February 2023 until April 2024. We analyzed the outcomes of patient who did vs did not receive bridging XRT pre- CAR-T lymphodepletion and infusion.

Results:

Fifty patients received Axi-cel in our institution during the study period, of whom, 13 patients received bridging XRT. The median follow up was 7.6 months or 228.5 days (25-475). The baseline characteristics were similar between the XRT & no XRT group. Median age was 53.5 years (17-78), 30 patients (60%) were males, ECOG was 1 or less in 43 pts (86%). CART was used as a third line or beyond in 9 patients (69%) in the XRT group, vs in 22 patients (59.5%) in the no XRT group.

The ORR & CR by day +90 were both 77% in the XRT group (10 of 13 pts). In the no XRT group, day +90 ORR was 51.4% (19 pts of 37) & CR was 43.2% (16 of 37 pts). At 12 months, the estimated PFS in the XRT group was 76%, vs. 47% in no XRT group (P=0.051). At 12 months, the estimated overall survival (OS) in the XRT group was 88.9%, vs. 72.1 % in the no XRT group (p= 0.299).

The median radiation dose was 28 Gy (range 9-30). The median number of fractions was 10 fractions (range 4-17). The most frequent radiation site was the mediastinum, n=5 (38.5%), of whom, 3 patients had Primary mediastinal B Lymphoma.

In the XRT group, all 13 patients (100%) experienced Cytokine Release syndrome CRS and all were grade I/II. In the no XRT group, 33 patients (89%) had CRS with 2 pts (6%) being grade III/IV CRS. Immune effector cells associated neurotoxicity syndrome ICANS occurred in 7 patients (54%) of the XRT group and in 12 patients in the no XRT group (32.4%). Grade III/IV ICANS was reported in 3 pts (43%) vs 8 pts (66.7%) in the XRT vs no XRT groups, respectively.

Conclusion:

Bridging Radiation therapy prior to anti-CD19 CART Axi-cel appears to be a promising strategy to improve outcomes. Further studies are needed to understand the interaction of XRT with CART, perhaps at the molecular level, with the potential benefit of avoiding further systemic therapy to preserve the fitness of T-cell prior to CAR-T infusion.

Saad:Kite: Consultancy; Sanofi: Consultancy. Alfayez:Amgen: Consultancy, Honoraria, Speakers Bureau; Biologics: Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Astellas: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Johnson & Johnson: Consultancy, Honoraria, Research Funding, Speakers Bureau; Abbvie: Consultancy, Honoraria, Research Funding, Speakers Bureau.