KEYNOTE-087: Pembrolizumab Monotherapy for Relapsed/Refractory Classical Hodgkin lymphoma

Written by Dr. Chepsy Philip from Believers Church Medical College Hospital, Tiruvalla, Kerala, India

KEYNOTE-087 is a multicentre, single-arm, multicohort, nonrandomized, phase 2 study of pembrolizumab in patients with R/R cHL who were ineligible for or progressed after ASCT and/or BV (Brentuximab). Previous reports demonstrated effective antitumor activity and a favourable safety profile in this subset of patients. The group now report on long term data with a follow up > 5 years. (1)

In brief, the trial enrolled patients into 3 cohorts: patients who did not respond to or progressed after ASCT and subsequent BV (cohort 1); patients who were unable to achieve a response (i.e., complete response [CR] or partial response [PR]) to salvage chemotherapy, did not receive ASCT, and progressed after BV (cohort 2); and patients who did not respond to or whose disease progressed after ASCT and did not receive subsequent BV (cohort 3). All patients in the study received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years or until disease progression (PD). The primary end points were safety and objective response rate (ORR) assessed per the 2007 International Working Group Revised Response Criteria for Malignant Lymphomas (IWG 2007) using blinded independent central review (BICR).

With a median follow-up of 63.7 months. ORR was 71.4% (95% confidence interval [CI], 64.8-77.4; CR, 27.6%; partial response, 43.8%). Median duration of response (DOR) was 16.6 months; median progression-free survival was 13.7 months. There are also some possible predictors of long-term response. All patients in the long-term response group (>4 years) were complete responders, and conversely, among patients achieving CR, more than half remained in CR after 4 years. Among those who relapse following CR, retreatment with pembrolizumab provides a high probability (74%) of achieving a second remission, possibly making this an excellent choice of therapy.

Though the duration of treatment was limited to 2 years with KEYNOTE-87, the remissions are comparable with the previously reported Checkmate 205 (treatment continued till progression) study; potentially informing that there might be no apparent benefit of continuing PD-1 blockade treatment beyond 2 years in patients with R/R cHL (2). In summary, the current report confirms the robust antitumor activity and manageable safety of pembrolizumab in R/R cHL.

1. Armand P, Zinzani PL, Lee HJ, Johnson NA, Brice P, Radford J, et al. Five-year follow-up of KEYNOTE-087: pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma. Blood. 2023 Sep 7;142(10):878–86.
2. Ansell SM, Bröckelmann PJ, von Keudell G, Lee HJ, Santoro A, Zinzani PL, et al. Nivolumab for Relapsed or Refractory (r/R) Classical Hodgkin Lymphoma (chl) After Autologous Transplantation: 5-Year Overall Survival from the Phase 2 Checkmate 205 Study. Hematol Oncol [Internet]. 2021 [cited 2023 Sep 10];39(S2). Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/hon.74_2879