Abstract P032

ABVD versus a risk-stratified and a response adapted strategy– addressing the dilemma in Advanced Hodgkin Lymphoma: A Phase III Randomized Study

Background: Outcomes with ABVD in advanced-stage cHL remain suboptimal in resource-limited settings. Although escBEACOPP improves disease control, concerns regarding toxicity and resource utilization limit its use. We evaluated a risk-stratified, response-adapted (RS/RA) strategy based on International Prognostic Score (IPS) and interim PET response against standard ABVD in a phase III randomized study.

Methods: Patients aged 15–60 years with newly diagnosed advanced-stage cHL were enrolled. They were randomized 1:1 to receive standard ABVD (Arm A) or a risk-stratified, response-adapted strategy (Arm B) using RATHL (IPS 0-2) and GHSG HD18 (IPS 3-7) approaches with interim PET-guided treatment modification. The primary endpoint was 3-year modified PFS, defined as progression, relapse, death, non-complete response, or initiation of subsequent anticancer therapy.

Results: Between September 2022 and July 2024, 200 patients were enrolled; 2 were excluded for protocol ineligibility, and 198 patients were analysed. The median age was 27 years (range, 15–58), and 140 (70.7%) were male. Baseline characteristics included B symptoms in 154 (77.8%), ECOG performance status 0–1 in 181 (91.4%), extranodal disease in 116 (58.5%), bulky disease in 82 (41.4%), stage III/IV disease in 169 (85.3%), and high-risk patients were 53/99 in Arm A and 56/99 in Arm B. The 3-year mPFS was 79.1% (95% CI, 71.2-87.7) in Arm A and 83.0% (95% CI, 75.7-91.0) in Arm B (p=0.53). The 3-year OS was 96.8% (95% CI, 93.3–100.0) and 93.6% (95% CI, 88.2–99.3), respectively (p=0.72). After a median follow-up of 38 months (range, 1–63), 37 events were observed, including 20 in Arm A and 17 in Arm B (including 1 death due to septic shock). The median time to relapse was 9.9 months (range, 1.9–37.1). Post relapse 15/36 patients received a nivolumab based regimen as salvage and 11/36 patients received bone marrow transplantation. No new safety signals were observed. Six patients receiving escBEACOPP were switched to ABVD/AVD due to toxicity. In Arm B, 3 low-risk patients had a positive interim PET scan and were escalated to escBEACOPP, of whom 2 subsequently had progressive disease.

Conclusion: Standard ABVD achieved comparable outcomes to RS/RA strategy, with no significant differences between the groups. However, the final results comparing patient reported outcomes and resource utilization will help determine the optimal frontline treatment strategy for advanced cHL.