Role of consolidation RT to bulky lesions of advanced Hodgkin lymphoma: results of FIL HD0801 trial

Purpose or Objective: The role of consolidation radiotherapy (RT) to bulky lesions after chemotherapy is controversial in advanced stage Hodgkin's lymphoma (HL) patients obtaining a complete metabolic response with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) regimen. Herein we present the final results of the phase III randomized part of the Italian Lymphoma Foundation (FIL) HD0801 trial, which investigated the potential benefit of consolidation RT in patients achieving a complete metabolic response at the end of the pre-planned 6 cycles of ABVD. Material and Methods: Overall, 512 patients with advanced-stage HL were recruited in the HD0801 trial. The phase II part of the study evaluating the efficacy of an early PET-guided salvage treatment, consisting of high-dose chemotherapy with a subsequent autologous stem cell transplant, was previously published. Patients who completed ABVD regimen and achieved a complete metabolic response were then randomized in the phase III part to receive or not consolidation RT to bulky lesions at baseline, defined as any mass with a maximum diameter of 5 cm. Results: In all, 354 patients had a PET negative finding after 6 ABVD. Of these, 116 (32.7%) had a bulky lesion at baseline and were randomly assigned to RT or no further treatments (NFT). Median bulky diameter was similar for RT and NFT arms (8.1 vs 8.2 cm, respectively). The “intention-to-treat” analysis showed a similar progression free survival (PFS) at 3 and 5 years between RT arm (86% and 83.7%, respectively) and NFT arm (85.8% at both time-points). Notably, 9 patients enrolled in the RT arm did not receive consolidative radiation (physician's decision), with 5 of them relapsing during follow up. Therefore, after correction with a “per-protocol” analysis, consolidation RT provided a PFS benefit of 10.3% at 3 years (91.7% vs 81.4) and of 7.5% at 5 years (88.9% vs 81.5%) compared to NFT (Figure), without achieving a statistical significance (p = 0.24) mainly because of the limited sample and number of events (5 vs 13, respectively). After stratification for the maximum diameter of the bulky lesion (<7 cm vs 7-10 cm vs >10 cm) we were not able to discriminate an optimal cut-off for the prediction of PFS. Figure: Progression free survival according to “per-protocol” analysis [Figure Presented] Conclusion: Advanced stage HL patients achieving a complete metabolic response after ABVD regimen may benefit from the addition of consolidation RT to bulky lesions at baseline, regardless of the maximum diameter of the mass, with a PFS benefit ranging from 7% to 10% at 3 and 5 years.