Immune Checkpoint Inhibitors Show Promise in B-Cell Lymphomas After HSCT
Research presented at the 2018 BMT Tandem Meetings (February 21-25, 2018; Salt Lake City, UT) showed that potential role of immune checkpoint inhibitors in the post-transplant setting for patients with relapsed or large B-cell lymphomas.
While outcomes for patients with relapsed or refractory B-cell lymphoma remain poor, patients who undergo a stem cell transplant benefit from improved outcomes. There have been few studies to evaluate immune checkpoint inhibitors in the pre- or post-transplant setting for diffuse large B-cell lymphoma.
John Sweetenham, MD, FRCP, FACP, senior director of clinical affairs, executive medical director, Huntsman Cancer Institute, University of Utah, presented the range of studies to analyze the effects of immune checkpoint inhibitors in B-cell lymphomas.
An analysis of ipilimumab by Ansell and colleagues in 2009 demonstrated tolerability and antitumor activity in patients with B-cell lymphoma. Among the 18 patients with diffuse large B-cell lymphoma included in the study, one patients achieved complete response for over 31 months.
Lesokhin and colleagues showed an 18% overall response rate and a 27% stable disease rate among patients with diffuse-large B-cell lymphoma treated with nivolumab (2016).
Another trial conducted by Zinzani and colleagues in 2017 demonstrated a 6% complete response rate and a 31% partial response rate among patients with relapsed or refractory primary mediastinal B-cell lymphoma treated with pembrolizumab.
Dr Sweetenham explained that while data in the pre-transplant setting have shown activity with immune checkpoint inhibitors in combination with salvage chemotherapy and radiation regimens, there may be an even greater rationale for checkpoint inhibitors in the post-transplant period, due to the opportunity to “eradicate remaining chemotherapy-refractory cells.”
In an abstract presented at the American Society of Hematology Annual Meeting and Exposition, Alan P Skarbnik and colleagues showed preliminary safety and efficacy data from an ongoing phase I study involving ipilimumab and nivolumab following autologous hematopoietic stem cell transplantation for 25 patients with high-risk hematologic malignancies. Researchers observed a 92% overall survival rate and an 88% progression-free survival rate after a median follow-up of 24 weeks. All of the patients with primary refractory diffuse large B-cell lymphoma were in complete response and there were no new safety signals as a result of the treatment.
“Overall, at the moment the data are extremely preliminary, but they do demonstrate the potential of the use of checkpoint inhibition in this disease, particularly in the post-transplant setting,” Dr Sweetenham said in his presentation. “The rationale for that is strong, based on minimal residual disease and the remodeling of the immune system.”
Numerous studies remain ongoing in this setting, including a phase II analysis of pembrolizumab following autologous hematopoietic stem cell transplantation for patients with relapsed or refractory Hodgkin lymphoma, diffuse large B-cell lymphoma, and peripheral T-cell lymphoma.—Zachary Bessette