Dr. Kremyanskaya on the Next Steps of the MANIFEST Trial in Myelofibrosis

Marina Kremyanskaya, MD, PhD, assistant professor of medicine, hematology, and medical oncology, Icahn School of Medicine, Mount Sinai, medical director, Inpatient Oncology Unit, The Mount Sinai Hospital, discusses the next steps of the phase 1/2 MANIFEST trial (NCT02158858) in myelofibrosis.

Updated findings from arm 1 of the MANIFEST trial demonstrated clinical and exploratory activity with the oral small molecule inhibitor of bromodomain 1/2 of BET proteins, pelabresib in patients with advanced myelofibrosis who were refractory to, ineligible for, or intolerant of ruxolitinib (Jakafi). 

The trial is ongoing, and patients are still being enrolled to arm 1 of the study, Kremyanskaya says. Therefore, additional efficacy data will emerge, as well as findings from centrally-reviewed bone marrow samples regarding fibrosis and bone marrow pathology.

Additionally, the MANIFEST trial led to the development of the phase 3 MANIFEST-2 trial (NCT04603495) in which patients with JAK inhibitor–naïve myelofibrosis will be randomized 1:1 to receive ruxolitinib plus pelabresib vs ruxolitinib plus placebo. The results will determine whether combining pelabresib with ruxolitinib can induce longer and deeper responses compared with single-agent therapy, Kremyanskaya concludes.