Assessing the role of radiotherapy in patients with refractory or relapsed high-grade B-cell lymphomas treated with CAR T-cell therapy

An estimated 30-40% of patients with diffuse large B cell lymphoma (DLBCL) will either relapse or have refractory disease with first-line chemoimmunotherapy. The standard approach for relapsed/refractory disease is salvage chemotherapy followed by autologous stem cell transplantation, but this approach cures fewer than 20% of patients in the modern era. This low cure rate is a result of refractory disease despite salvage therapy, medical ineligibility for transplantation, or relapse following transplantation. CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment paradigm for patients with relapsed or refractory disease, leading to response rates that range between 52% to 93%, and overall survival rates at one year between 48% and 83%. However, the time from apheresis to infusion of CAR T-cell therapy currently takes several weeks, leaving many patients in need of bridging therapy to control disease progression. Radiation therapy (RT) has been utilized as a bridging therapy prior to CAR T infusion in select patients, with some remarkable responses in chemorefractory disease. Furthermore, the potential synergy between RT and CAR T-cells due to immunomodulatory mechanisms has generated considerable excitement, as it has been hypothesized that RT could also be considered as a salvage therapy following CAR T failure, based on limited case series published to date. Prospective trials are warranted to validate the significance of this modality following CAR T-cell therapy.