Incorporating radiation with anti-CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory non-Hodgkin lymphoma: A multicenter consensus approach.

in American journal of hematology by Omran Saifi, Scott C Lester, William G Breen, William G Rule, Yi Lin, N Nora Bennani, Allison Rosenthal, Javier Munoz, Hemant S Murthy, Mohamed A Kharfan-Dabaja, Jennifer L Peterson, Bradford S Hoppe

TLDR

  • Radiation therapy (RT) can help improve the outcomes of patients with B-cell non-Hodgkin lymphoma who are undergoing anti-CD19 chimeric antigen receptor T-cell therapy (CART). Bridging RT before CART can control the disease during the manufacturing period, improve response rates and local control, reduce the severity of cytokine release syndrome, and prolong disease-free intervals and survival. Consolidative RT after CART can alter the pattern of relapse and improve local recurrence-free and progression-free survivals. Salvage RT for relapsed post-CART disease can have favorable survival outcomes. However, more research is needed to understand the best timing and dosing of RT and to develop personalized treatment plans based on individual patient characteristics and disease biology.

Abstract

Anti-CD19 chimeric antigen receptor T-cell therapy (CART) has revolutionized the outcomes of relapsed and/or refractory B-cell non-Hodgkin lymphoma. However, CART is still limited by its availability, toxicity, and response durability. Not all patients make it to the CART infusion phase due to disease progression. Among those who receive CART, a significant number of patients experience life-threatening cytokine release syndrome toxicity, and less than half maintain a durable response with the majority relapsing in pre-existing sites of disease present pre-CART. Radiation therapy stands as a promising peri-CART and salvage treatment that can improve the outcomes of these patients. Evidence suggests that bridging radiotherapy prior to CART controls the disease during the manufacturing period, augments response rates and local control, cytoreduces/debulks the disease and decreases the severity of cytokine release syndrome, and may prolong disease-free intervals and survival especially in patients with bulky disease. Consolidative radiotherapy for residual post-CART disease alters the pattern of relapse and improves local recurrence-free and progression-free survivals. Salvage radiotherapy for relapsed post-CART disease has favorable survival outcomes when delivered comprehensively for patients with limited relapsed disease and palliates symptoms for patients with diffuse relapsed disease. The biology of the disease during the peri-CART period is poorly understood, and further studies investigating the optimal timing and dosing of radiation therapy (RT) are needed. In this review, we tackle the most significant challenges of CART, review and propose how RT can help mitigate these challenges, and provide The Mayo Clinic experts' approach on incorporating RT with CART.

Overview

  • The study focuses on the use of anti-CD19 chimeric antigen receptor T-cell therapy (CART) for relapsed and/or refractory B-cell non-Hodgkin lymphoma. The hypothesis being tested is the effectiveness of radiation therapy (RT) in improving the outcomes of patients undergoing CART. The methodology used for the experiment includes a review of existing literature on the use of RT in conjunction with CART for B-cell non-Hodgkin lymphoma. The primary objective of the study is to provide a comprehensive review of the current state of RT and CART for B-cell non-Hodgkin lymphoma and to propose potential solutions to the challenges associated with CART, such as availability, toxicity, and response durability.

Comparative Analysis & Findings

  • The study compares the outcomes of patients undergoing CART with and without RT. The results show that bridging RT prior to CART controls the disease during the manufacturing period, augments response rates and local control, cytoreduces/debulks the disease and decreases the severity of cytokine release syndrome, and may prolong disease-free intervals and survival especially in patients with bulky disease. Consolidative RT for residual post-CART disease alters the pattern of relapse and improves local recurrence-free and progression-free survivals. Salvage RT for relapsed post-CART disease has favorable survival outcomes when delivered comprehensively for patients with limited relapsed disease and palliates symptoms for patients with diffuse relapsed disease.

Implications and Future Directions

  • The study's findings suggest that RT can improve the outcomes of patients undergoing CART for B-cell non-Hodgkin lymphoma. However, further studies investigating the optimal timing and dosing of RT are needed to fully understand the biology of the disease during the peri-CART period. The Mayo Clinic experts propose a comprehensive approach to incorporating RT with CART, which includes bridging RT prior to CART, consolidative RT for residual post-CART disease, and salvage RT for relapsed post-CART disease. Future research should focus on developing personalized RT and CART treatment plans based on individual patient characteristics and disease biology.
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