Consolidative Radiotherapy Remains a Key Player in the Salvage Management of Hodgkin Lymphoma

Abstract

The role of radiotherapy following high dose chemotherapy and autologous stem cell transplantation (ASCT) for relapsed or refractory Hodgkin lymphoma (HL) has not been addressed in a prospective randomized trial. While the benefit of consolidative radiotherapy has been demonstrated in other clinical settings for HL, concern of late radiotherapy associated toxicity and uncertain treatment efficacy remain as deterrents in the peritransplant setting.We retrospectively reviewed patients with relapsed or refractory HL who underwent high dose chemotherapy and an ASCT from 2000-2019 at our institution. The association of clinicopathologic factors with the delivery of consolidative radiotherapy was assessed by Chi squared analysis. Kaplan Meier and a cox regression analysis were used to estimate factors independently associated with progression-free survival (PFS) and overall survival (OS).From 2000-2019, 179 consecutive patients underwent salvage chemotherapy (most commonly ICE: ifofsamide, carboplatin, and etoposide) followed by high dose chemotherapy (most commonly BEAM: BCNU, Etoposide, Ara-C and Melphalan) and an autologous stem cell transplant for relapsed (63.4%) or refractory (36.6%) HL with a median follow up of 59.4 months. Post-transplant consolidative radiotherapy was delivered to a median dose of 3600 cGy in 20 fractions to 72 patients (40.2%). Consolidative radiotherapy was associated with younger age (median age 32 vs. 42 years, P < 0.001), stage I-II disease at the time of salvage chemotherapy (76.4% vs 52.3%, P = 0.001), and no prior radiotherapy (76.4% vs 45.8%, P < 0.001). On univariate analysis, consolidative radiotherapy was associated with an improved two-year PFS (84.1% vs 64.1%, P = 0.005) and OS rates (95.7% vs 80.8%, P = 0.017). In the Cox regression analysis, consolidative radiotherapy was significantly associated with improved PFS (HR: 0.492, 95% CI: 0.288-0.84, P = 0.009) along with ECOG performance status < 2 (HR: 0.188, 95% CI: 0.045-0.79, P = 0.022), achieving a complete response to salvage chemotherapy (HR: 0.463, 95% CI: 0.233-0.92, P = 0.028), and stage I-II disease (HR: 0.546, 95% CI: 0.325-0.918, P = 0.022). Similarly, consolidative radiotherapy was associated with significantly improved OS (HR: 0.398, 95% CI: 0.205-0.771, P = 0.006) along with ECOG performance status < 2 (HR: 0.073, 95% CI: 0.016-0.333, P = 0.001). Following transplantation, grade ≥2 pneumonitis was identified in 10 patients (5.6%) of which only 7 patients underwent consolidative radiotherapy which was delivered to mediastinal (50.0%), supraclavicular (10.0%), or abdominal (10.0%) fields. No patient deaths were associated with pneumonitis.Our findings suggest that consolidative radiotherapy in the salvage management of HL is associated with improved PFS and OS with low rates of treatment associated complications. Further investigation in the role of consolidative radiotherapy in this setting is warranted.