A Pooled Analysis of Differences in Salvage Therapy for Early-Stage Hodgkin’s Lymphoma with PET Directed Omission of Radiotherapy

Abstract

De-escalation in early-stage Hodgkin’s Lymphoma (HL) with the omission of radiotherapy (RT) in PET responders has been extensively studied with multiple international randomized studies showing a consistent improvement in progression-free survival with no difference overall survival. Higher rates of progression generally indicate that patients will need salvage chemotherapy ±autologous stem cell transplant to maintain equivalent overall survival, a difference not well highlighted in the current literature. We aimed to better quantify this difference in salvage treatment with a meta-analysis of available randomized trials. A comprehensive Medline and conference abstracts search was performed, identifying 4 prospective studies of early-stage HL with randomization to ±RT in PET responders (Picardi et al, EORTC H10, UK RAPID, German HD16). Authors from included studies were contacted for patient level data, of which Picardi et al provided additional data. The meta-analysis was carried out using commercially available software. Odds ratio (OR) was used to estimate effects size for salvage therapies. A total of 2772 patients (RT: n = 1641, no RT: n = 1131) were included. The use of any type of second line therapy was 11.7% (n = 132/1131) in the no RT group versus 3.7% (n = 61/1641) in the RT group (OR = 3.24; 95% CI 2.37-4.44, p<0.00001). High dose chemotherapy with autologous stem cell transplant use was 6.5% (n = 74/1131) in the no RT group versus 2.7% (n = 45/1641) in the RT group (OR = 2.48; 95% CI 1.70-3.64, p<0.00001). Second line chemotherapy and/or RT use was 4.7% (n = 53/1131) in the no RT group versus 0.9% (n = 14/1641) in the RT group (OR = 4.94; 95% CI 2.76-8.87, p<0.00001). Salvage RT alone was 2.1% (n = 11/511) in the no RT group versus 0.2% (n = 1/537) in the RT group (OR = 8.21; 95% CI 1.49-45.35, p = 0.02). Antibody therapy use was 0.2% (n = 1/511) in the no RT group versus 0.2% (n = 1/537) in the RT group (OR = 1.04; 95% CI 0.15-7.32, p = 0.97). Omission of RT in early-stage PET-negative HL carries a 3.2-fold increase in requiring any form of salvage therapy and a 2.5-fold increase in salvage autologous transplant. These increases in therapy and attendant toxicities should be discussed with patients when considering strategies of chemotherapy alone versus combined modality in early-stage HL.