HL

KEYNOTE-087 phase II results: Pembrolizumab shown to be effective when given once every three weeks in relapsed/refractory Classical Hodgkin Lymphoma (cHL)

In April in The Journal of Clinical Oncology, Robert Chen, from the City of Hope National Medical Center, Duarte, California, and colleagues published the results of the KEYNOTE-087 phase II trial into the efficacy and safety of pembrolizumab, a PD1-inhibitor, in the treatment of relapsed or refractory classical Hodgkin lymphoma.

The study was a single-arm, multicenter trial which included three patient cohorts, each with a different treatment background. The primary endpoint was ORR by blinded independent central review and safety. In all cohorts a dose of 200mg pembrolizumab was given by I.V. once every three weeks for a maximum of 24 months.

Key Highlights:
  • Patients enrolled = 210 with a median of four prior lines of therapy
    • Cohort 1: Disease progression after Autologous Stem Cell Transplant (ASCT) and Brentuximab Vedotin (BV) (n = 69)
    • Cohort 2: Disease progression after salvage chemotherapy and BC, and ineligible for ASCT (n = 81)
    • Cohort 3: Disease progression after ASCT without BV treatment (n = 60)
  • Efficacy:
    • Median duration of follow-up = 10.1 months, median 13 cycles of treatment
    • Overall ORR = 69% (95% CI, 62.3–75.2%)
      • Cohort 1 = 73.9% (95% CI, 61.9–83.7%)
      • Cohort 2 = 64.2% (95% CI, 52.8–74.6%)
      • Cohort 3 = 70.0% (95% CI, 56.8–81.2%)
    • Overall CRR = 22.4% (95% CI, 16.9–28.6%)
      • Cohort 1 = 21.7% (95% CI, 12.7–33.3%)
      • Cohort 2 = 24.7% (95% CI, 15.8–35.5%)
      • Cohort 3 = 20.0% (95% CI, 10.8–32.3%)
    • Median DoR and OS not reached
    • Nine-month OS = 97.5%, PFS = 63.4%
  • Safety
    • Most common grade 3/4 treatment related AEs: neutropenia (2.4% pts), dyspnea (1% pts) and diarrhea (1% pts).
    • Infusion related reactions and immune-mediated AEs occurred in 28.6% pts
    • Discontinuations due to treatment-related AEs = 4.3%
    • Two patients died, neither death related to treatment

The authors stated that there is an unmet need for R/R cHL patients, especially in those who are transplant-ineligible or relapsed after transplantation. In this study, the authors concluded, pembrolizumab was shown to have “substantial clinical activity in subsets of heavily pre-treated patients” and further support the potential role of PD-1 inhibition in cHL. A randomized phase III trial is ongoing (KEYNOTE-204).

Abstract:

Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 (ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response ≥ 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.

Reference:
  1. Chen R. et al. Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. Journal of Clinical Oncology. 2017 Apr 25. DOI: 1200/JCO.2016.72.1316 [Epub ahead of print].