The Role of Radiotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Post-CAR-T Therapy: A Systematic Literature Review

Abstract

IntroductionHistorically, the management of relapsed or refractory diffuse large B-cell lymphoma (r/r-DLBCL) involved chemotherapy and autologous stem cell transplant, though outcomes were often suboptimal. Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the therapeutic landscape for r/r-DLBCL, achieving high response rates and improving progression-free and overall survival. However, a significant proportion of patients relapse after CAR-T, and optimal treatment strategies for post-CAR-T relapse remain unclear. Radiotherapy (RT), a highly effective treatment for lymphoma, is increasingly recognized for its potential role as both a bridging therapy and a salvage option following CAR-T relapse.MethodsA comprehensive literature review was conducted using databases including PubMed, Scopus, EMBASE, and Cochrane Library, with search terms combining "radiotherapy," "radiation therapy," "lymphoma," and "CAR T-cell." A total of 690 records were screened, and 14 studies were included in the analysis after applying inclusion and exclusion criteria.ResultsRT demonstrates high response rates in CAR-T relapsed DLBCL, with overall response rates (ORR) ranging from 35% to 82.4% and complete response rates (CRR) from 17% to 59%. One-year local control rates ranged between 62% and 84%. Salvage RT showed comparable or superior outcomes to systemic therapies in multiple studies, particularly in patients with localized relapses. The toxicity profile of RT was favorable, particularly when modern techniques such as IMRT were employed. Case reports and retrospective series highlighted its effectiveness in achieving durable responses and controlling localized disease progression.ConclusionsRadiotherapy is a safe and effective treatment option for patients with DLBCL relapsed or refractory after CAR-T therapy. It achieves high local control rates and favorable outcomes, particularly in patients with localized relapse. Incorporating RT into the therapeutic workflow may enhance the management of this challenging population. Further prospective studies are needed to define its role and optimize treatment sequencing.

Keywords: CAR-T; CAR-T CELL; DLBCL; LYMPHOMA; RADIATION THERAPY; RADIOTHERAPY; refractory; relapsing; salvage.

Figure 1.

Workflow Adopted for Selecting the Records to Include in the Final Literature Review.