Checkpoint inhibitors are effective in the treatment of Hodgkin’s lymphoma

Results of two phase I studies indicate that blocking ‘programmed death protein-1’ (PD-1) activity is an effective way to treat patients with classical Hodgkin’s lymphoma (cHL). In a first study, the PD-1 inhibitor nivolumab was shown to be associated with a complete remission rate of 87% in 23 patients with heavily pretreated, relapsed or refractory cHL. Similarly, a second phase I study demonstrated that pembrolizumab, another PD-1 inhibitor, induced a response in 20 of 29 heavily pre-treated patients with cHL (66%). All patients in this study failed previous treatment with brentuximab vedotin, and 69% of patients enrolled had relapsed after a stem cell transplant. These data underline the potential of PD-1 inhibition in the management of cHL and form the basis for larger phase II or III clinical trials.

cHL is characterized by Reed Sternberg (RS) cells surrounded by an extensive, but ineffective inflammatory/immune cell infiltrate. Recent studies suggest that Hodgkin RS cells have developed mechanisms that exploit the programmed cell death-1 (PD-1) pathway to evade immune detection. The two phase I studies at hand hypothesized that blocking the PD-1 signal from reaching the immune cells might restore their anti-cancer activity.

In the first study, 23 patients with relapsed or resistant cHL were treated with nivolumab. Seventy eight percent of the patients in this study had failed more than three previous treatment regimens, including stem cell transplant (78%) and brentuximab vedotin (78%). All patients received an intravenous infusion of nivolumab every two weeks until their tumors progressed or they experienced excessive toxicity. At the time of the last analysis and after an average follow up of 40 weeks, 20 of the 23 patients (87%) receiving nivolumab had experienced either a complete response (four patients, 17%) or a partial response (16 patients, 70%). All 23 patients had a reduction in their tumor burden at one or more efficacy assessments during treatment with nivolumab. Among the 18 patients who had previously failed brentuximab vedotin, the overall response rate was 89% (16/18), with 6% (1/18) achieving a complete response and 83% (15/18) having a partial response. The progression-free survival rate at 24 weeks was 86% and the median overall survival was not yet reached. The drug’s toxicity mirrored that observed in other solid tumor cancers, with no life-threatening toxicity, and 22% of patients experiencing a serious treatment-related adverse event.1

In the second study, the PD-1 inhibitor pembrolizumab was evaluated in 29 heavily pre-treated patients with cHL. All patients in this study failed previous treatment with brentuximab vedotin, and 69% of patients enrolled had relapsed after a stem cell transplant. Patients received pembrolizumab intravenously every two weeks until disease progression, excessive toxicity, or completion of two years of therapy. At the time of analysis in November 2014, 66% of the patients responded to the drug, with six patients (21%) achieving a complete remission and 13 patients (45%) achieving a partial response. Pembrolizumab appeared to be well-tolerated, as there were no serious treatment-related adverse events. Three patients experienced moderate treatment-related adverse events.2

The data of these two studies are encouraging for Hodgkin’s lymphoma patients with relapsed or treatment-resistant disease. The positive response rates seen in these phase I trials validate the scientific hypothesis that Hodgkin lymphoma relies heavily on the PD-1 pathway for survival.


  1. Armand P, Ansell S, Lesokhin A, et al. Nivolumab in Patients with Relapsed or Refractory Hodgkin’s Lymphoma - Preliminary Safety, Efficacy and Biomarker Results of a Phase I Study. Presented at ASH 2014; Abstract #289.
  2. Moskowitz C, Ribrag V, Michot JM, et al. PD-1 Blockade with the Monoclonal Antibody Pembrolizumab (MK-3475) in Patients with Classical Hodgkin’s Lymphoma after Brentuximab Vedotin Failure: Preliminary Results from a Phase 1b Study (KEYNOTE-013). Presented at ASH 2014; Abstract #290.

Speaker Philippe Armand


Philippe Armand, MD, PhD,
Harvard Medical School, Dana-Farber Cancer Institute, Boston, USA


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