Programmed death-1 blockade with pembrolizumab in patients with classical hodgkin lymphoma after brentuximab vedotin failure

Purpos Classical Hodgkin lymphoma (HL) frequently exhibits genetic alterations leading to overexpressio of the programmed death-1 (PD-1) ligands, suggesting a possible vulnerability to PD-1 blockade. Th phase Ib study KEYNOTE-013 (NCT01953692) tested the safety and efficacy of the anti-PD-antibody pembrolizumab in patients with hematologic malignancies. Based on its genetics, HL wa included as an independent cohort Method We enrolled patients with relapsed or refractory HL whose disease progressed on or after treatmen with brentuximab vedotin. Patients received pembrolizumab, 10 mg/kg every 2 weeks, until diseas progression occurred. Response to treatment was assessed at week 12 and every 8 week thereafter. Principal end points were safety and complete remission (CR) rate Result Thirty-one patients were enrolled; 55% had more than four lines of prior therapy, and 71% ha relapsed after autologous stem cell transplantation. Five patients (16%) experienced grade 3 drugrelate adverse events (AEs); there were no grade 4 AEs or deaths related to treatment. The CR rat was 16% (90% CI, 7% to 31%). In addition, 48% of patients achieved a partial remission, for a overall response rate of 65% (90% CI, 48% to 79%). Most of the responses (70%) lasted longer tha 24 weeks (range, 0.14+ to 74+ weeks), with a median follow-up of 17 months. The progression-fre survival rate was 69% at 24 weeks and 46% at 52 weeks. Biomarker analyses demonstrated a hig prevalence of PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural kille cells, and activation of interferon-g, T-cell receptor, and expanded immune-related signaling pathways Conclusion Pembrolizumab was associated with a favorable safety profile. Pembrolizumab treatment induce favorable responses in a heavily pretreated patient cohort, justifying further studies.