PD-1 Inhibition and the Changing Frontline Landscape of Advanced Classical Hodgkin Lymphoma: A Narrative Review with a Focus on Applicability in Lower- and Middle-Income Settings

Abstract

Frontline management of advanced-stage classical Hodgkin lymphoma (cHL) has been transformed by PET adapted therapy, brentuximab vedotin (BV)-based regimens, and PD-1 blockade; however, drug cost and infrastructure barriers constrain translation to lower- and middle-income countries (LMICs). We conducted a narrative review of phase II–III trials and real-world studies (PubMed, Embase, ClinicalTrials.gov; 2010–2026). PET-adapted strategies permit safe de-escalation in interim-PET–negative patients. BV-AVD (ECHELON-1) and BrECADD (HD21) improve progression-free survival over ABVD and escalated BEACOPP. Nivolumab AVD (S1826) is now the preferred standard, achieving 2-year PFS of 92% versus 83% with BV-AVD. The January 2026 launch of the world’s first nivolumab biosimilar in India — at approximately one-third the reference price — makes N-AVD economically accessible in LMICs for the first time. BV-containing regimens, lacking a biosimilar, remain prohibitively expensive. This shift has fundamentally altered the feasibility of trial quality care in resource-constrained settings. Post-marketing biosimilar surveillance in cHL and LMIC registries are urgently needed.