John O. Mascarenhas, MD, discusses emerging agents in myelofibrosis.
John O. Mascarenhas, MD, associate professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai; director of the Adult Leukemia Program; and leader of Clinical Investigation within the Myeloproliferative Disorders Program at Mount Sinai, and a member of the Tisch Cancer Institute, discusses emerging agents in myelofibrosis.
The BET inhibitor CPI-0610 and the BCL-2 inhibitor navitoclax have demonstrated efficacy in phase 2 clinical trials as monotherapy or in combination with ruxolitinib (Jakafi) in patients with refractory or intolerant advanced myelofibrosis, says Mascarenhas. The agents were shown to improve splenomegaly and symptom burden, as well as bone marrow fibrosis and anemia in a subset of patients, Mascarenhas explains.
As such, CPI-0610 and navitoclax are being evaluated in the frontline setting to determine if adding them to ruxolitinib could improve the efficacy demonstrated in the second-line setting, Mascarenhas says. For example, CPI-0610 in combination with ruxolitinib is being evaluated for patients with treatment-naïve myelofibrosis vs ruxolitinib plus placebo in the phase 3 MANIFEST-2 trial (NCT04603495). The hope is that the addition of CPI-0610 will deepen splenic and symptom responses, while reducing bone marrow fibrosis and anemia that is associated with JAK inhibition, concludes Mascarenhas.