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

Area of Science:

• Hematology
• Oncology
• Radiation Oncology

Background:

• Bridging radiotherapy (Br-RT) is increasingly used before chimeric antigen receptor T-cell therapy (CAR-T) for relapsed/refractory B-cell lymphomas (r/r BCL).
• The impact of Br-RT on CAR-T efficacy and toxicity in this setting is not well understood.

Purpose of the Study:

• To evaluate the efficacy and toxicity of Br-RT followed by CAR-T in patients with r/r BCL.
• To identify factors associated with improved outcomes in this high-risk patient population.

Main Methods:

• Retrospective review of 172 patients with r/r BCL who received Br-RT followed by CAR-T from 2018-2020 across 10 institutions.
• Toxicity assessment using CTCAE v5.0 and ASTCT Consensus Guidelines for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
• Multivariable analysis to identify predictors of progression-free survival (PFS) and overall survival (OS).

Main Results:

• Grade ≥3 Br-RT toxicity occurred in 2% of patients; grade ≥3 CRS in 9%; grade ≥3 ICANS in 24%.
• Two-year PFS was 38% and OS was 53%.
• Comprehensive Br-RT was associated with superior PFS (HR 0.38) and OS (HR 0.48). LDH normalization post-Br-RT also correlated with improved PFS and OS.

Conclusions:

• Br-RT prior to CAR-T in high-risk r/r BCL patients demonstrates an acceptable toxicity profile and favorable clinical outcomes.
• Comprehensive Br-RT and post-Br-RT LDH normalization may be associated with superior PFS and OS, warranting further investigation.