Dr. Verstovsek on the Rationale Behind Treating Myelofibrosis With CPI-0610/Ruxolitinib

Srdan Verstovsek, MD, PhD, discusses research efforts being made with CPI-0610 in the treatment of patients with myelofibrosis.

Srdan Verstovsek, MD, PhD, the United Energy Resources, Inc. Professor of Medicine, director of the Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms, and chief of the Section for Myeloproliferative Neoplasms in the Department of Leukemia of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses research efforts being made with CPI-0610 in the treatment of patients with myelofibrosis.

In the study, CPI-0610 is being investigated as an add-on to ruxolitinib in patients with advanced myelofibrosis who have experienced a suboptimal response to ruxolitinib as a single agent. CPI-0610 is a BET inhibitor and anepigenetic modifier, says Verstovsek. Epigenetic abnormalities are often present in patients with myelofibrosis and can be associated with a loss of response to JAK inhibitors or progression on JAK inhibitors, which shortens the life expectancy of patients. The idea of utilizing epigenetic modifiers is not new; it has been studied with hypomethylating agents, such as azacitidine and decitabine. Now, LSD1, BET, and PRMT5 inhibitors are available; they all modify genetic expression in different ways, adds Verstovsek.

This particular agent is being evaluated in multiple ways in patients with myelofibrosis in multiple studies. The agent has been evaluated in a single-agent arm in this phase 2 study; it has also been examined after a JAK inhibitor in the second-line setting. This agent has also been given to patients who are on a stable dose of ruxolitinib (Jakafi) in an add-on approach or by combining these agents from the very beginning in the first-line setting. There are then separations within subgroups based on the goal of the therapy or the reason why patients are enrolling on a study. Two examples of such goals include improving anemia or improving quality of life in patients, concludes Verstovsek.