Matching-adjusted indirect treatment comparison of A+AVD vs PET-guided ABVD in newly diagnosed advanced Hodgkin lymphoma

AIMS: The study team investigated the relative efficacy of brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) versus positron emission tomography (PET)-guided doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) among previously untreated adults with advanced Hodgkin lymphoma via matching-adjusted indirect comparison (MAIC). MATERIALS & METHODS: A systematic literature review identified ECHELON-1 (A+AVD), RATHL, and SWOG S0816 as feasible trials referencing a targeted comparator (PET-guided ABVD). Effect modifiers/prognostic variables were identified by clinical expert opinion and Cox regression using long-term ECHELON-1 individual patient-level data. Weighted Cox regressions generated hazard ratios (HR) and 95% confidence intervals (CI) representing A+AVD versus PET-guided ABVD relative treatment effect on overall survival (OS) and progression-free survival (PFS). RESULTS: OS improved significantly with A+AVD versus PET-guided ABVD (HR [95% CI] 0.48 [0.32, 0.73], p < 0.001 [RATHL]; 0.49 [0.26, 0.92], p = 0.043 [SWOG S0816]). PFS significantly favored A+AVD over PET-guided ABVD in both trial comparisons. While the proportional hazards assumption did not hold for these comparisons, 8-year restricted mean survival time and piecewise Cox regression results aligned with the main results. CONCLUSION: MAIC results indicated durable A+AVD treatment benefits in adults with newly diagnosed advanced Hodgkin lymphoma versus PET-guided regimens evaluated in RATHL and SWOG S0816.