BrECADD Improves PFS Vs Nivolumab/AVD in Advanced-Stage Hodgkin Lymphoma

A treatment regimen containing brentuximab vedotin (Adcetris), etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD) displayed favorable progression-free survival (PFS) outcomes vs nivolumab (Opdivo) plus doxorubicin, vinblastine, and dacarbazine (AVD) among patients 18 years and older with advanced-stage Hodgkin lymphoma, according to a matching-adjusted indirect treatment comparison (MAIC) of the phase 3 HD21 (NCT02661503)and SWOG S1826 trials (NCT03907488), presented at the European Hematology Association (EHA) 2026 Congress.

Among patients 18 years and older, the BrECADD regimen conferred significantly improved PFS vs nivolumab/AVD, with an HR of 0.58 (95% CI, 0.36-0.92; P = 0.029). Among patients 18 to 60 years of age, which consisted of all patients who were randomly assigned in the HD21 protocol, the HR for PFS was 0.48 (95% CI, 0.29-0.81; P = 0.010), supporting BrECADD. Conversely, among patients older than 60 years, a minimal improvement in PFS was observed with nivolumab/AVD; the HR for PFS was 1.05 (95% CI, 0.39-2.80; P = 0.925).

Moreover, compared with the SWOG S1826 intent-to-treat (ITT) population, which included patients 12 years and older, BrECADD demonstrated a significant improvement in PFS, with an HR of 0.56 (95% CI, 0.35-0.88; P = 0.015). In the sensitivity analysis, BrECADD was consistently favored regardless of covariate adjustments tested or censoring timepoint cutoffs applied for the 18 years and older or 18-to-60-year populations.

“BrECADD delivers significantly improved PFS vs [nivolumab/AVD] in the [18 and older and 18-to-60] advanced Hodgkin lymphoma populations in MAIC analyses with mature follow-up data,” Alexa Molinari, PharmD, MD, global health economics lead at Takeda Oncology, wrote in the publication with study coinvestigators. “Interpretation of results for patients [60 years and older] was challenging given small sample sizes and limited events, even with additional long-term follow-up. Analyses based on 5-year data confirm the survival benefit demonstrated in the 3-year results, reinforcing the robustness of this comparison which can be used to inform healthcare decision-making.”

The investigators of the MAIC gathered pooled individual patient-level data (IPD) from the randomized and non-randomized cohorts of the HD21 trial, which were weighed for comparison with aggregate SWOG S1826 data using an unanchored approach. Moreover, prognostic variables and effect modifiers were identified through a literature review, as well as consultations with clinical experts and a prespecified statistical analysis. Additionally, baseline characteristics including age, sex, International Prognostic Score, and disease stage were adjusted to inform base-case comparisons.

The investigators of the study sought to assess PFS via unanchored MAIC to estimate the long-term efficacy of BrECADD vs nivolumab/AVD across key age subgroups, given the availability of IPD from the HD21 5-year data cutoff and aggregate data from SWOG S1826.

The study authors noted several limitations with the analysis. Regarding data-related limitations, reporting of the baseline characteristics differed between studies:

• Mean age was not reported in the SWOG S1826 protocol
• Differences in follow-up time may have contributed to informative censoring bias
• Approximations were required due to the limited data accessibility of the 3-year SWOG S1826 data
• The studies had distinct geographical differences, limiting the generalizability of the results

Moreover, the investigators noted that long-term toxicities in younger patients may inform treatment decision-making processes, but safety outcomes could not be consistently assessed due to a lack of available data.

The study authors also touched upon limitations associated with indirect trial comparison, noting that unanchored MAICs are more susceptible to bias and systematic errors vs anchored MAICs. Moreover, they highlighted that Kaplan-Meier survival curves could not perfectly replicate true IPD, with a pseudo-IPD being generated for the SWOG S1826 trial to provide reasonable estimates to re-create numerical values.

Reference

Molinari A, Kristo F, Melchardt T, et al. Comparison of long-term efficacy between the BrECADD and N+AVD regimens in advanced-stage Hodgkin lymphoma: a matching-adjusted indirect treatment comparison of the HD21 and SWOG S1826 trials. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract PS2017.