PD-1 Blockade with Pembrolizumab for Classical Hodgkin Lymphoma after Autologous Stem Cell Transplantation
Mené sur 30 patients atteints d'un lymphome hodgkinien classique réfractaire ou récidivant, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression à 18 mois, et la toxicité du pembrolizumab en traitement de consolidation après une greffe autologue de cellules souches hématopoïétiques
PD-1 blockade using pembrolizumab administered after autologous stem cell transplantation has an acceptable safety profile.This treatment results in a high PFS in patients with classical Hodgkin lymphoma, including in high-risk patients. Autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed/refractory classical Hodgkin lymphoma (RR cHL) who respond to salvage chemotherapy. However, relapse after ASCT remains a frequent cause of treatment failure, with poor subsequent prognosis. Since cHL is uniquely vulnerable to PD-1 blockade, PD-1 blockade given as consolidation after ASCT could improve ASCT outcomes. We therefore conducted a multi-cohort phase 2 study of pembrolizumab in patients with RR cHL after ASCT, hypothesizing that it would improve the progression-free survival (PFS) at 18 months after ASCT (primary endpoint) from 60% to 80%. Pembrolizumab was administered at 200mg IV every 3 weeks for up to 8 cycles, starting within 21 days of post-ASCT discharge. 30 patients were treated on this study. The median age was 33, and 90% were high-risk by clinical criteria. 77% completed all 8 cycles. Toxicity was manageable, with 30% of patients experiencing at least 1 grade 3 or higher adverse event (AE), and 40% at least 1 grade 2 or higher immune-related AE. 2 pts were lost to follow-up in complete remission at 12 months. The PFS at 18 months for the 28 evaluable patients was 82%, meeting the primary endpoint. The 18-month overall survival was 100%. In conclusion, pembrolizumab was successfully administered as post-ASCT consolidation in patients with RR cHL, and resulted in a promising PFS in a high-risk patient cohort, supporting the testing of this strategy in a randomized trial. This trial is registered at clinicaltrials.gov (NCT02362997).