A Blog from the Lymphoma Program at Weill Cornell Medicine and NewYork-Presbyterian
Investigators from around the world are taking notice of our results in treating patients with mantle cell lymphoma. (MCL) In the below video, Dr. Laurie Sehn from the University of British Columbia shares her thoughts on Dr. Jia Ruan’s clinical trial of lenalidomide plus rituximab for previously untreated mantle cell lymphoma.
In the following video Dr. Ruan further discusses results of her trial with lenalidomide and rituximab combination for patients with MCL.
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.
Just over one year ago, in November 2013, the United States Food and Drug Administration (FDA) approved the oral drug ibrutinib for patients with previously treated mantle cell lymphoma (MCL). The FDA based its decision upon promising results from the PCYC-1104 trial that took place at several centers around the world, including Weill Cornell Medical College (WCMC). During the 56th Annual Meeting of the American Society of Hematology, long-term follow up from the PCYC-1104 trial was presented. At the two year time point, roughly one third of patients remain free from progression. Moreover, serious side effects appear to become less frequent with time.
Because bias and chance can sometimes lead to promising results, investigators from around the world, including WCMC performed a second trial (MCL2001) to evaluate the effects, good and bad, of ibrutinib in 120 patients with previously treated MCL. Preliminary data from MCL2001 was also presented during ASH, and they appear to be consistent with the PCYC-1104. With roughly 15 months of follow up, two-thirds of patients responded and responses lasted for a little more than one year on average. No new side effects were identified.
Finally, preliminary results from the MCL4001 Early Access Program (EAP), were presented. The EAP was designed to provide ibrutinib to patients with relapsed or refractory MCL prior to its approval by the FDA and was open at several sites around the world, including WCMC. One hundred forty-nine patients with MCL received daily oral ibrutinib and were followed for safety. Like the PCYC-1104 and MCL2001 trials, MCL4001 confirmed the safety of ibrutinib. Less than 10% of patients stopped ibrutinib due to an adverse event and most patients continued to receive ibrutinib through the EAP until the FDA approved it. Taken together, these three trials confirm the important role of ibrutinib in the management of mantle cell lymphoma.
Unfortunately, despite the recognized efficacy of ibrutinib in patients with MCL, roughly one-third of patients are resistant and among those that respond, secondary resistance to ibrutinib is common. In a retrospective cohort study we identified 32 patients at WCMC and Ohio State University, who experienced progression of lymphoma while receiving ibrutinib. There was no clear association between prior number of therapies, ibrutinib response, morphology, Ki67 prior to ibrutinib, response to ibrutinib, duration of ibrutinib, or choice of subsequent therapy and overall survival. Ultimately primary and secondary ibrutinib resistance was associated with poor clinical outcomes, and there were no identifiable predictors of response to subsequent therapy following development of ibrutinib resistance.
These data underscore the importance of ongoing research in MCL. As we learn more about potential mechanisms of resistance to ibrutinib we are able to design rational combinations that build on the remarkable safety and activity of the drug. Moreover, there is clearly a need for new treatments that have the potential to help patients that experience progression of lymphoma while on ibrutinib. Fortunately, investigators at WCMC and around the world have identified the emergence of this new unmet need and are working on new treatment options. Stay tuned to the WCMC Lymphoma Program Blog for new developments.
New Developments in Lymphoma 