Radiation Therapy for Relapsed or Refractory Diffuse Large B-Cell Lymphoma: What Is the Right Regimen for Palliation?

PURPOSE: To report objective response rates (ORR), time to local failure (TTLF), and overall survival (OS) among patients with relapsed or refractory diffuse large B-cell lymphoma after salvage- or palliative-intent radiation therapy (RT) and to investigate whether outcomes differed with conventional versus hypofractionated (≥2.5 Gy/fraction) RT. METHODS AND MATERIALS: A single-institution observational cohort study was performed for patients who completed a course of RT for relapsed or refractory diffuse large B-cell lymphoma between January 1, 2008, and April 1, 2020. Predictors of ORR, TTLF, and OS were calculated using univariable and multivariable regression models. The Kaplan-Meier method was used to estimate TTLF and OS, and log-rank analysis was used to compare outcomes. Equivalent dose in 2 Gy fractions (EQD2) was calculated using an α/β of 10. RESULTS: One-hundred and sixty-nine patients were treated with 205 RT courses (73 [36%] salvage, 132 [64%] palliative), and hypofractionated RT was used in 100 RT courses (49%). Median RT dose was 30 Gy (range, 8-60 Gy). ORR was 60% for the total cohort (53% and 69% for palliative and salvage cohorts, respectively). Over a median follow-up time of 4 months, median OS in all patients was 5 months (3 and 22 months for palliative and salvage cohorts, respectively). No statistically significant differences in ORR, TTLF, and OS were observed with hypofractionation compared with conventional fractionation. EQD2 ≥35 Gy was associated with improved ORR (odds ratio, 3.79 [1.19-12.03]; P = .024) and prolonged TTLF (0.39 [0.18-0.87]; P = .022), while double-hit receptor status (8.18 [1.08-62.05]; P = .042), cell of origin (3.87 [1.17-8.74]; P = .0012), and bulky disease (≥7.5 cm; 2.12 [1.18-3.81]; P = .012) were associated with inferior TTLF. In the palliative-only cohort, a low-dose regimen of 8 Gy in 2 fractions was associated with similar ORR compared with other fractionation schema but trended towards inferior TTLF (P = .36). CONCLUSIONS: Hypofractionation is not associated with differences in disease outcomes for patients with relapsed or refractory diffuse large B-cell lymphoma, while higher RT dose (EQD2 ≥35 Gy) may improve ORR and TTLF. Future work is warranted to elucidate the ideal dose and fractionation schema for such patients who will likely also undergo novel systemic agents and cellular therapies.