Abstract P031

Multistate Modeling of Disease Trajectories for Advanced-Stage Hodgkin Lymphoma Patients Receiving PET Response-Adapted Therapy

Background: Despite recent advances in advanced-stage (AS) classical Hodgkin lymphoma (cHL), PET-adapted chemotherapy remains a first-line option where access to novel agents is limited. Many regimens begin with 2 cycles of escalated BEACOPP (escBEACOPP2) or ABVD (ABVD2), followed by interim PET (iPET)-guided treatment. There have been no direct comparisons of PET-adapted regimens initiated with escBEACOPP2 vs ABVD2. We used rigorous multistate model (MSM) methodology to assess transition specific impacts of treatment (escBEACOPP vs ABVD), baseline HL International Prognostic Index (A-HIPI) risk score, and iPET result.

Methods: We pooled individual data from 4 clinical trials of newly-diagnosed stage IIB-IV cHL patients (ages 18-60 years (y)) treated with PET-adaptive escBEACOPP2 (n=363 from AHL2011) or ABVD2 (n=1917 from SWOG0816, RATHL, HD0607) regimens. The 5y MSM implemented with a Cox model had 4 states: diagnosis, sustained remission at 1y, treatment failure, and death. We assessed the impact of treatment on transitions (except binary sustained remission at 1y) that involved ≥5 pts per group, adjusting for A-HIPI for all transitions and iPET for post-remission transitions.

Results: The escBEACOPP2 group was younger (age 32 (SD 11) vs 34 y (SD 11)), had fewer females (39% vs 47%), less stage IIB disease (12% vs 28%), more bulk (57% vs 25%), and higher baseline disease risk according to A-HIPI (25.1 (SD 6.3) vs 22.7 (SD 6.3)). After adjusting for A-HIPI, escBEACOPP2 was associated with lower hazard of treatment failure within 1y (aHR 0.61, 95%CI 0.40-0.93) and post-remission failure (aHR 0.39, 95%CI 0.22-0.6; see Table). Negative iPET was associated with lower hazards of post-remission failure (aHR 0.55, 95%CI 0.38–0.78) and death after first-line treatment failure (aHR 0.57, 95%CI 0.35–0.91), independent of baseline A-HIPI score and initial chemotherapy.

Conclusions: iPET-adapted treatment with escBEACOPP was associated with lower rates of both early treatment failure and post-remission relapse versus ABVD, after adjustment for baseline disease risk. Negative iPET was independently associated with a lower risk of post-remission treatment failure and death following frontline treatment failure, regardless of chemotherapy regimen or A-HIPI score. MSM offers a dynamic assessment of disease trajectories by capturing transitions between remission, treatment failure and death, and it provides a comprehensive framework to inform clinical decision-making.