Michael E. Williams, MD, ScM reviewing Chen R et al. J Clin Oncol 2017 Apr 25.

Two thirds of patients responded to treatment with the immune checkpoint inhibitor.

Classical Hodgkin lymphoma (cHL) frequently overexpresses the programmed death-ligands 1 and 2 (PD-L1 and PD-L2), usually by gene amplification or other alterations at the chromosome 9p24.1 locus or via Epstein-Barr virus infection. As a result, high response rates have been observed with immune checkpoint inhibitors that target the PD-1/PD-L1 pathway in relapsed or refractory patients.

To evaluate the clinical activity of the immune checkpoint inhibitor pembrolizumab in this setting, investigators conducted an industry-sponsored, single-arm, phase II study (KEYNOTE-087) in which heavily pretreated patients with relapsed or refractory cHL received 200 mg of pembrolizumab once every 3 weeks for a maximum of 24 months or until disease progression or significant toxicity. PD-L1 expression was determined by immunohistochemistry, and responses and toxicity were verified by blinded independent central review.

The median treatment duration was 8.3 months, the overall response rate was 69%, and the complete remission rate was 22.4%. Ten patients proceeded to allogeneic stem cell transplantation (SCT), and 4 proceeded to autologous SCT. The 9-month progression-free survival was 63.4%. The most common treatment-related adverse events were hypothyroidism (12.4%) and fever (10.5%); 4.3% of patients discontinued treatment due to severe adverse events (cardiac, pneumonitis, infusion reactions, or cytokine release syndrome). Clinical activity was seen across all levels of PD-L1 expression.

CITATION(S):

Chen R et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol 2017 Apr 25; [e-pub].

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