Advertisement

PD-1 Blockade with Pembrolizumab for Classical Hodgkin Lymphoma after Autologous Stem Cell Transplantation

Philippe Armand, Yi-Bin Chen, Robert A Redd, Robin M Joyce, Jad Bsat, Erin Jeter, Reid W Merryman, Kimberly C Coleman, Parastoo B. Dahi, Yago Nieto, Ann S. LaCasce, David C. Fisher, Samuel Y. Ng, Oreofe O Odejide, Arnold S. Freedman, Austin I Kim, Jennifer L. Crombie, Caron A. Jacobson, Eric D. Jacobsen, Jeffrey L. Wong, Sanjay S Patel, Jerome Ritz, Scott J. Rodig, Margaret A Shipp and Alex F. Herrera

Key Points

  • 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.

Abstract

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).

  • Submitted February 18, 2019.
  • Revision received March 25, 2019.
  • Accepted April 2, 2019.