Do you know how to use immune checkpoint inhibitors to treat a variety of hematologic malignancies? Test yourself with our latest quiz.
A.Classical Hodgkin lymphoma
In March 2016, the first FDA approval of a PD-1 immune checkpoint inhibitor for a hematologic malignancy was the agency’s approval of nivolumab for treatment of patients with classical Hodgkin lymphoma who had experienced disease progression or relapse after autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin. PD-1 is a cell surface receptor involved in downregulation of immune inflammatory response and immune self-tolerance. Its activity enables some cancer cells to evade the immune system.
C. Adult T-cell leukemia/lymphoma
Lee Ratner, MD, PhD, of the Washington University School of Medicine in St. Louis, and coauthors reported that the first three patients in a phase II clinical trial of immunotherapy for adult T-cell leukemia/lymphoma experienced rapid disease progression following a single treatment dose of the PD-1 monoclonal antibody nivolumab.
C.Allogeneic stem cell transplantation
Despite evidence that immune checkpoint inhibition can be efficacious in patients with relapsed acute myeloid leukemia after allogeneic stem cell transplantation, some experts have voiced concern about the potential for immune checkpoint inhibition to incite acceleration of GVHD after allogeneic transplantation for acute lymphoblastic leukemia and other hematologic malignancies. Further study is required to evaluate the role of immune checkpoint inhibition in patients with different hematologic cancers who experience relapse after allogeneic stem cell transplantation.
In late 2017, the FDA placed partial clinical holds on several studies of immune checkpoint inhibitor regimens for relapsed or refractory multiple myeloma, including nivolumab, durvalumab, and pembrolizumab and atezolizumab, following the discontinuation of three clinical trials of pembrolizumab combination therapies. The roles of immune checkpoint inhibition in multiple myeloma management are not yet clear.
Counterintuitively, the predictive value of cancer cell expression of PD-1 in different malignancies remains unclear. However, cancer genome mutational burden does appear to be associated with responses to immune checkpoint inhibition, at least in part because tumors with more mutations express more highly antigenic cell-surface neoantigens. Hematologic malignancies generally appear to harbor fewer somatic mutations than do solid tumors.