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Multicenter Study
. 2025 Jul 8;9(13):3293-3303.
doi: 10.1182/bloodadvances.2025015855.

Bridging radiotherapy before chimeric antigen receptor T cells for B-cell lymphomas: an ILROG multicenter study

Nikhil Yegya-Raman  1 , John P Plastaras  1 , Christopher M Wright  1   2 , Monica Chelius  1 , Siqi Zhang  3 , Jonathan A Baron  1 , Harper Hubbeling  1   4 , Austin J Sim  5   6 , Timothy J Robinson  5   7 , Michael D Jain  8 , Brandon Imber  4 , Beatrice Fregonese  4 , Joachim Yahalom  4 , Colton Ladbury  9 , Savita Dandapani  9 , Chelsea C Pinnix  10 , Jillian R Gunther  10 , Penny Q Fang  10 , Susan Y Wu  10 , Bouthaina S Dabaja  10 , Joanna C Yang  11 , Jessica Chew  12 , Steve Braunstein  12 , Sumi Sinha  12 , Nathan M Delinger  13 , Susan Sun  14 , Stephanie A Terezakis  14 , Gukan Sakthivel  15 , Louis S Constine  15 , Amit K Chowdhry  15 , Patrick M Reagan  16 , Skyler Burke  17 , Yolanda D Tseng  17 , Michael J LaRiviere  1 , Amit Maity  1   18 , Stephen J Schuster  19   20 , Elise A Chong  19   20 , Nicholas B Figura  6
Affiliations
Multicenter Study

Bridging radiotherapy before chimeric antigen receptor T cells for B-cell lymphomas: an ILROG multicenter study

Nikhil Yegya-Raman et al. Blood Adv. .

Abstract

Despite the increasing utilization of bridging radiotherapy (Br-RT), its impact on chimeric antigen receptor T-cell therapy (CAR-T) efficacy and toxicity remains poorly characterized. We retrospectively reviewed patients with relapsed/refractory B-cell lymphomas (BCLs) who received Br-RT followed by CAR-T from 2018 to 2020 across 10 institutions. Br-RT toxicities were graded per Common Terminology Criteria for Adverse Events version 5.0, and cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per American Society for Transplantation and Cellular Therapy Consensus Guidelines. One hundred seventy-two patients (168 large BCL) received Br-RT before axicabtagene ciloleucel (73%), tisagenlecleucel (24%), or brexucabtagene autoleucel (2%). At leukapheresis, most patients (74%) had advanced-stage disease and 39% had bulky disease measuring ≥10cm. Comprehensive Br-RT was administered to 39% and bridging systemic therapy to 35%. Among all patients, grade ≥3 Br-RT toxicity occurred in 2% (1 grade 5 toxicity), grade ≥3 CRS in 9%, and grade ≥3 ICANS in 24%. Median follow-up was 31.3 months. Two-year progression-free survival (PFS) and overall survival (OS) were 38% and 53%, respectively. On multivariable analysis, comprehensive Br-RT was associated with superior PFS (hazard ratio [HR], 0.38; P < .001) and OS (HR, 0.48; P = .011). Patients with lactate dehydrogenase (LDH) normalization after Br-RT (high pre-Br-RT LDH, normal post-Br-RT LDH) had superior PFS and OS compared with those with high post-Br-RT LDH and similar PFS and OS compared with those with normal baseline LDH. In this particularly high-risk cohort, Br-RT before CAR-T demonstrates an acceptable toxicity profile with favorable clinical outcomes compared with historical controls. Comprehensive Br-RT and LDH normalization after Br-RT may be associated with superior PFS and OS.

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Conflict of interest statement

Conflict-of-interest disclosure: E.A.C. reports research funding from Genmab, AbbVie, AstraZeneca, CARGO, Genentech/Roche, and Nurix, and has consulted for AstraZeneca, BeiGene, Genmab, and AbbVie. N.M.D. reports research funding from Bristol Myers Squibb and serves on the advisory board for Miltenyi Biotec. S.J.S. reports research funding from Genentech/Roche, Genmab, and Nurix; has consulted for AbbVie, AstraZeneca, BeiGene, BioNTech, Genentech, Genmab, Janssen, Kite Pharmaceuticals, Legend Biotech, MorphoSys, and Novartis; and serves on steering committees for Caribou Biosciences and Novartis. P.M.R. reports research funding from Genentech and Seagen; has consulted for Caribou Biosciences and Kite Gilead; and has received speaking fees from Kite Gilead. M.J.D. reports research funding from Kite Gilead, Incyte, and Eli Lilly, and has consulted for and provides advisory to Kite Gilead and Novartis. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Best response to CAR-T by 3 months (N = 168 evaluable). CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease.
Figure 2.
Figure 2.
Patterns of treatment failure (N = 86 evaluable) with respect to lesions present from preleukapheresis scans up to CAR-T infusion (preexisting lesions, new lesions, or both; left) and with respect to Br-RT fields (in-field, out-of-field, or both; right).
Figure 3.
Figure 3.
Disease outcomes among all patients (N = 176). (A) PFS and (B) OS.
Figure 4.
Figure 4.
Prognostic value of LDH changes after bridging therapy among all evaluable patients (N = 157). (A) Sankey diagram depicting preleukapheresis (prebridging therapy) and preinfusion (postbridging therapy) LDH (high vs normal for each). (B) PFS and (C) OS stratified by LDH category.
Figure 5.
Figure 5.
CAR-T toxicity (CRS and ICANS) among all patients (N = 172).
See this image and copyright information in PMC

References

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