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

Future Oncol. 2026 Mar;22(7):843-852. doi: 10.1080/14796694.2025.2609296. Epub 2026 Jan 12.

Abstract

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.

Keywords: Hodgkin lymphoma; Matching-adjusted indirect comparison; brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine; doxorubicin, bleomycin, vinblastine, and dacarbazine; overall survival; positron emission tomography-guided; progression-free survival.

Plain language summary

What is this summary about?Hodgkin lymphoma is a rare blood cancer that affects the lymphatic system. Advanced Hodgkin lymphoma occurs when the lymphoma spreads to other sites in the body beyond the lymphatic system. In stage III, the lymphoma has spread to the lymph nodes above and below the diaphragm. In this study, the scientists aimed to compare the effectiveness of treatments in adults with newly diagnosed advanced Hodgkin lymphoma. The treatments compared included combinations of drugs, “brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine” (“A+AVD”) and “doxorubicin, bleomycin, vinblastine, and dacarbazine” (“ABVD”). ABVD is given to adults with advanced Hodgkin lymphoma based on the results of a nuclear medicine imaging examination called positron emission tomography (“PET-guided”). As these treatments have not been directly compared in clinical trials, the study team used mathematical techniques to compare them indirectly using information from clinical trials. The clinical trials that were suitable for comparison included one that looked at how effective A+AVD is at treating patients with advanced Hodgkin lymphoma, called ECHELON-1, as well as two studies that looked at how effective PET-guided ABVD is at treating patients with advanced Hodgkin lymphoma, called RATHL and SWOG S0816.What were the results?The results showed that adults with advanced Hodgkin lymphoma had better survival and less progression/worsening of their cancer if treated with A+AVD versus PET-guided ABVD.What do the results mean?The results of this study could help provide doctors, patients with advanced Hodgkin lymphoma, and their families/caregivers with information related to treatment decision-making.

Publication types

  • Comparative Study
  • Systematic Review
  • Review

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bleomycin / administration & dosage
  • Brentuximab Vedotin / administration & dosage
  • Dacarbazine / administration & dosage
  • Doxorubicin / administration & dosage
  • Female
  • Hodgkin Disease* / diagnosis
  • Hodgkin Disease* / diagnostic imaging
  • Hodgkin Disease* / drug therapy
  • Hodgkin Disease* / mortality
  • Hodgkin Disease* / pathology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Positron-Emission Tomography* / methods
  • Prognosis
  • Treatment Outcome
  • Vinblastine / administration & dosage

Substances

  • Dacarbazine
  • Vinblastine
  • Bleomycin
  • Doxorubicin
  • Brentuximab Vedotin

Supplementary concepts

  • ABVD protocol