Clinical efficacy and safety of pembrolizumab and nivolumab in frontline treatment for classical Hodgkin lymphoma: systematic review and meta-analysis of clinical trials.

Abstract

Treatment of classical Hodgkin lymphoma (cHL) underwent substantial advances throughout the last decades, where PD-1 inhibitors showed improved clinical outcomes, leading to their approval for relapsed and refractory disease. Recent studies showed benefit in utilizing these agents in first-line settings. Recent studies showed benefit in utilizing these agents in first-line settings. This meta-analysis investigates clinical efficacy and safety of pembrolizumab and nivolumab for frontline cHL treatment. A comprehensive literature search was conducted through PubMed, EBSCO Host, and CENTRAL using relevant keywords. Full-text publications in the English language of clinical trials were selected. Complete response rate (CRR), overall response rate (ORR), 2-year overall survival (OS), 2-year progression-free survival (PFS), and grade ≥3 adverse events (AEs) were evaluated for pooled analysis. Nine trials, including 880 patients with previously untreated cHL (21% with early-stage disease) with a median age of 34 years and a median follow-up of 31.2 months, were analyzed. Pooled data in all treatments revealed ORR 86% (95% confidence interval (CI), 59-96%), CRR 57% (95% CI, 62-97%), 2-year PFS 90% (95% CI, 70-97%), and 2-year OS 97% (95% CI, 91%-99%). Forty-one percent of patients (95% CI, 21-64%) experienced grade ≥3 AEs, and 17% (95% CI, 6-38%) grade ≥3 immune-related AEs in all treatment groups. AVD with pembrolizumab or nivolumab showed comparable efficacy (2-year PFS: 97% (95% CI, 88-99%) vs 92% (95% CI, 89-94%), 2-year OS: 98% (95% CI, 88%-100%) vs 99% (95% CI, 99-100%) and safety (grade ≥3 AEs: 36% vs 33%), respectively. Nivolumab with brentuximab vedotin had worse outcomes (2-year PFS 80%, OS 87%, and grade ≥3 AEs 79%), likely due to an older study population (median age 71.5 years). Adoption of nivolumab or pembrolizumab combinations in frontline treatment for cHL is a valid strategy for advanced disease or patients who are unfit or not interested in intensive cytotoxic chemotherapy regimens.