Combination of brentuximab vedotin and nivolumab in the management of Hodgkin lymphoma: A systematic review and meta-analysis

Abstract Introduction: Hodgkin lymphoma is a type of cancer that affects the lymphatic system, characterized by the presence of Reed-Sternberg cells. Although the combination of Brentuximab Vedotin with Nivolumab is used in treating relapsed or refractory disease, there is limited cumulative evidence of its survival benefits and safety profile. This review and analysis aim to report survival benefits, progression-free interval, and overall safety profile. Method Following PRISMA guidelines, a comprehensive search of PubMed, Cochrane, Embase, Google Scholar, and ClinicalTrials.gov (inception to May 2025) was conducted using MeSH terms for “ Brentuximab Vedotin”, “Hodgkin Lymphoma”, and ” Nivolumab.” After screening and excluding review articles, meta-analyses, and studies without a patient population of interest, three studies reporting the outcomes of the combination of brentuximab vedotin and nivolumab in Hodgkin's lymphoma were selected for inclusion from a total of 1432 references. A random-effects model using dichotomous data with corresponding confidence intervals (CIs) was applied for each included study. Statistical heterogeneity was assessed using I2 statistics. All statistical analyses were conducted using Open Meta-Analyst. Some characteristics were described systematically. Results A total of 158 patients from 2 randomized controlled trials (RCTs) and one retrospective study were included in this analysis. The median age was 35 (range, 18-77), and 51% (n=81) were females. Among the reporting studies, 27% had prior radiotherapy (n = 31/112), 53% had an ECOG status of 0 (n = 72/137), and 42% had an ECOG status of 1 (n = 58/137). All patients had stage IV disease. The median treatment duration was 21.2 months (range, 1.8-47). The pooled rates for median progression-free survival (mPFS) and the median overall survival (mOS) were 56% (95% CI: 0.134–0.988; p = 0.001, I2 =93.4%) and 85% (95% CI: 0.801–0.910; p = 0.431, I2 =0.0%), respectively. The pooled rates for gastrointestinal side effects and elevated liver enzymes were 26% (95% CI -0.100 to 0.622) and 4.4% (95% CI -0.022 to 0.109, p = 0.007, I2 =79.59%). Respectively. The pooled rates for peripheral neuropathy and neutropenia/leukopenia were 32% (95% CI 0.025-0.617, p 0.001, I2 =92.33%) and 9.8% (95% CI -0.026 to 0.221, p = 0.128, I2 =56.92%), respectively. Conclusion This meta-analysis suggests that the combination of Brentuximab Vedotin and Nivolumab may improve survival and increase the progression-free interval in patients with advanced, relapsed, or refractory Hodgkin's lymphoma, with an acceptable safety profile. Future high-quality trials with larger patient populations are needed to consolidate these findings.