By Peter Martin, MD
On December 9, 2014 I wrote a brief post describing preliminary results from a phase II study of brentuximab vedotin as second-line therapy for Hodgkin lymphoma. The investigator-initiated study was performed jointly at City of Hope and Weill Cornell Medical College, highlighting a new era of collaboration between researchers working to improve the outcomes of people with lymphoma. The results of that study have now been published in the peer-reviewed journal Biology of Blood and Marrow Transplantation.
The purpose of the study was to evaluate the efficacy of brentuximab vedotin as second-line therapy in Hodgkin lymphoma (i.e., the lymphoma was not cured by first-line chemotherapy). Of the 37 study participants, almost half were able to proceed to potentially curative stem cell transplantation with brentuximab vedotin alone; i.e., no chemotherapy. Interestingly, all of the 13 patients that achieved a complete response with brentuximab vedotin did so within just 2 cycles (3 weeks).
This study suggests that brentuximab vedotin is efficacious in the second-line, pre-transplant setting, and that some patients may be spared cytotoxic chemotherapy prior to transplant. Moreover, responses seem to occur quickly in those people most likely to benefit, and there appears to be little rationale for continuing the same dose of brentuximab vedotin beyond 2 cycles in patients that have not achieved a complete response. Despite the clear activity of brentuximab vedotin in this setting, we do not advocate its use outside the context of a clinical trial until additional studies and longer follow up has been reported. Future studies will focus on combining brentuximab vedotin with other targeted agents with the intention of improving outcomes even more.
For more information about brentuximab vedotin look to this blog for further updates. If you are interested in Hodgkin lymphoma related clinical trials please visit our clinical trials listings.
The Weill Cornell Lymphoma Program has recently opened a new clinical trial for men and women with classical Hodgkin Lymphoma (cHL) subjects after failure of autologous stem cell transplant (ASCT). The study sponsor is Bristol-Myers Squibb, and the principal investigator at Weill Cornell is Dr. Lisa Roth. For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at firstname.lastname@example.org.
- Men and women age 18 and older
- Cohort A: Subjects not exposed to brentuximab vedotin
– Documented absence of complete response (CR) after 90 days from stem cell infusion for most recent ASCT; or
– Documented relapsed disease (after CR) or disease progression (after Partial Response (PR) or Stable Disease (SD))
- Cohort B: Subjects who failed treatment with brentuximab vedotin which was administered after failure of ASCT
– Documented failure to achieve at least PR after the most recent treatment; or
– Documented relapse disease (after CR) or disease progression (after PR or SD)
- Detailed eligibility reviewed when you contact the study team
This clinical trial is for men and women with classical Hodgkin Lymphoma who failed autologous stem cell transplant (ASCT). Subjects never treated with brentuximab vedotin are in Cohort A, or may have had prior brentuximab vedotin treatment as a salvage therapy after failure of ASCT are in Cohort B. The study is evaluating an experimental drug called nivolumab.
Nivolumab is in clinical development for the treatment of subjects with solid tumors and hematological (blood) malignancies. Nivolumab is an antibody (a type of human protein) that is being tested to see if it will allow the body’s immune system to work against tumor cells.
The purposes of this research study is to assess treatment with nivolumab with hopes that treatment with nivolumab will lead to clinical benefit, as demonstrated by a clinically meaningful objective response rate, including durable responses with substantial magnitude of tumor burden reduction in the heavily treated cHL subjects.
By Peter Martin, MD
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.