Hypereosinophilic syndrome and suspected myeloid neoplasia in relapsed Hodgkin lymphoma during immune checkpoint inhibitor therapy: a rare case

Abstract

Classic Hodgkin lymphoma (cHL) generally has favorable outcomes with frontline ABVD chemotherapy; however, 15-30% of advanced-stage patients experience relapse. While PD-1 inhibitors like pembrolizumab have shown promise in relapsed/refractory cHL, immune-related adverse events remain incompletely characterized. We report a 56-year-old male with stage IV nodular sclerosis cHL who relapsed after multiple treatment lines including ABVD, DHAP, brentuximab vedotin, and ICE. Following pembrolizumab plus GVD (gemcitabine, vinorelbine, liposomal doxorubicin), he achieved complete metabolic response. Subsequently, he developed marked leukocytosis (WBC: 63,000/μL) with profound eosinophilia (53,000/μL), meeting criteria for hypereosinophilic syndrome (HES). Molecular workup revealed FIP1L1-PDGFRA rearrangement in 2% of cells. The patient required hospitalization for dehydration, renal dysfunction, and anasarca, and was managed with corticosteroids after hydroxyurea intolerance. This case uniquely documents HES as a rare complication of pembrolizumab/GVD in multiply relapsed cHL, occurring after extensive prior therapy that may have contributed to its development. The molecular findings suggest potential therapeutic avenues. Clinicians should maintain vigilance for eosinophilia during PD-1 inhibitor therapy, as HES management may take precedence over ongoing immunotherapy.