Nivolumab and pembrolizumab are members of a class of drugs known as immune checkpoint inhibitors. Both drugs are monoclonal antibodies that bind to and inhibit the programmed death 1 receptor (PD-1) on the surface of T-cells, thereby improving the ability of the immune system to fight against cancer. The concept is especially attractive because it capitalizes on the ability of the immune system to fight cancer rather than relying on drugs that are toxic to cancer cells. Both drugs (as well as other immune checkpoint inhibitors) have demonstrated significant promise in various solid tumors (e.g., melanoma) but are only now entering the world of lymphoma. On December 7, during a morning session at the 56th annual meeting of the American Society of Hematology, we saw some early evidence of the promise that this class of drugs represents.
In the first abstract, Dr. Philippe Armand presented preliminary results from a phase I trial of nivolumab in patients with previously treated Hodgkin lymphoma (HL). These results were simultaneously published in the New England Journal of Medicine and led the FDA to grant nivolumab the breakthrough therapy designation for patients with relapsed/refractory HL. A total of 23 patients with relapsed or refractory HL were enrolled on the trial and every patient experienced reduction of tumor burden, including 70% achieving a partial response and 17% experiencing a complete response. Of the 18 patients who had previously received brentuximab vedotin, the overall response rate was 89%. Longer follow up will be required to better estimate the duration of benefit.
In a second abstract, Dr. Alexander M. Lesokhin presented the results from the same phase I trial of nivolumab in patients with relapsed or refractory lymphoid malignancies, including B-cell and T-cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). The overall response rate in patients with B-NHL was 28%, including 40% of patients with DLBCL. Nivolumab appeared less promising in patients with T-NHL and MM.
In a final abstract Dr. Craig H. Moskowitz presented preliminary results from a phase I trial with pembrolizumab in patients with Hodgkin lymphoma after failure of brentuximab vedotin. Almost 70% of patients had also previously received prior autologous stem cell transplantation and the median number of prior therapies was 4. The reported response rate was 53%, including a 20% complete response rate.
The results from these trials confirm the activity and safety of anti-PD-1 antibodies in patients with Hogkin and non-Hodgkin lymphomas. For information regarding ongoing trials at Weill Cornell Medical College with nivolumab for treatment of Hodgkin and non-Hodgkin lymphomas, follow the links for Hodgkin lymphoma, follicular lymphoma, and DLBCL, or contact us at (212) 746-1362. Look to this space for more news concerning nivolumab.