Radiation Therapy for Refractory High-grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements

Abstract

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement (HGBL-DH/TH) is an aggressive disease with inferior outcomes. We sought to evaluate the efficacy of radiation therapy (RT) for patients with HGBL-DH/TH treated for gross disease. We identified 80 patients treated with RT between 2013-2019 for refractory diffuse large B-cell lymphoma. Patients with CNS disease were excluded. Eligible patients had fluorescence in situ hybridization (FISH) confirmed HGBL-DH/TH with gross disease at the time of RT (defined as positron emission tomography-computed tomography [PET-CT] five-point scale [5PS] of 4-5 or progression on CT). RT intent was palliative (disease excluded from the field), salvage (all known disease encompassed), or bridging (RT prior to chimeric antigen receptor [CAR] T-cell therapy). Progression free survival (PFS), overall survival (OS) and local control (LC) were defined from the last day of RT. LC was defined as the absence of in-field recurrence and censored at the time of last follow up, out of field progression, or death. The in-field overall response rate (ORR) was defined as combined partial response (PR) and complete response (CR) within the RT field. We identified 27 HGBL-DH/TH patients. The median age was 63.5; 78% had primary refractory disease after frontline chemotherapy. The median number of systemic therapies (ST) prior to RT was 2 (range [R] 1-4). Intent of RT was palliative in 33% (n = 9), salvage in 59% (n = 14) and bridging in 15% (n = 4). The median RT dose was 42.5 Gy (R 8-60); 59% received a dose of ≥ 40 Gy (n = 16). Concurrent ST was given to 37% (n = 10). ST after RT was administered to 48% (n = 13); 37% (n = 10) received CAR T-cell therapy after RT. The median follow-up was 12.1 months. There were 20 recurrences (74%) and 18 deaths (67%, all due to lymphoma). The 1-year PFS and OS rates were 22.2% and 32.2% respectively. LC evaluation was possible for 25 patients. While the initial in-field ORR was 88% (CR, n = 12, PR, n = 10), the 1-year LC rate was only 43.8% with 11 in-field recurrences in total, either in the absence (n = 2) or presence of out of field progression (n = 9). LC was not impacted by RT doses of ≥40 Gy (p = 0.62); the median RT dose for patients with local failure was 46.7 Gy (R 24-60). There was no difference in PFS according to RT intent (p = 0.56), RT dose ≥ 40 Gy (p = 0.57), receipt of concurrent ST (p = 0.14), or receipt of ST after RT (p = 0.34). Similarly, OS was not impacted by these factors. However, patients that received CAR T-cell therapy after RT had a trend towards improved PFS (p = 0.07) and superior OS (p = 0.04). Patients with refractory HGBL-DH/TH have a poor prognosis. While initial in-field ORRs are high, even with RT doses ≥40 Gy, in and out-of-field progression is common. CAR T-cell therapy can be effective in this population. RT with a short, hypofractionated course may be a useful tool to permit disease temporization while CAR T-cell therapy is pursued.