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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 ASCT has an acceptable safety profile.

  • This treatment results in a high PFS in patients with cHL, including in high-risk patients.

Publisher's Note: There is a Blood Commentary on this article in this issue.

Abstract

Autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL) who respond to salvage chemotherapy. However, relapse after ASCT remains a frequent cause of treatment failure, with poor subsequent prognosis. Because cHL is uniquely vulnerable to programmed cell death-1 (PD-1) blockade, PD-1 blockade given as consolidation after ASCT could improve ASCT outcomes. We therefore conducted a multicohort 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 end point) from 60% to 80%. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles, starting within 21 days of post-ASCT discharge. Thirty patients were treated on this study. The median age was 33 years, and 90% were high-risk by clinical criteria. Seventy-seven percent 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. Two patients 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 end point. 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 was registered at www.clinicaltrials.gov as #NCT02362997.

  • Submitted February 18, 2019.
  • Accepted March 24, 2019.
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