Dr. Rampal on ACVR1 Inhibition With Pacritinib in Myelofibrosis

Raajit K. Rampal, MD, PhD, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discusses the investigation of ACVR1 inhibition as a mechanism for improving anemia in patients with myelofibrosis.

The phase 3 PERSIST 2 trial (NCT02055781) evaluated the safety and efficacy of pacritinib vs best available therapy in patients with thrombocytopenia and primary or secondary myelofibrosis. A retrospective analysis explored the agent’s effect on transfusion independence and hemoglobin in patients treated on the trial.

Prior results from the trial showed an improvement in hemoglobin for patients treated with pacritinib, prompting further study of the role of the agent as an inhibitor of ACVR1, Rampal says, adding that momelotinib, a JAK inhibitor under investigation in myelofibrosis, has demonstrated ACVR1 inhibition. The biochemical assays demonstrated that pacritinib inhibited ACVR1 on a nanomolar level similar to momelotinib, Rampal explains.

Furthermore, the retrospective analysis of PERSIST-2 showed that 15% and 23% of patients who were given 200-mg or 400-mg doses of pacritinib, respectively, and who had a baseline hemoglobin less than 10 g/dL experienced an improvement of at least 1 g/dL at any time through week 24 vs 7% of those who received best available therapy (BAT), Rampal says.

A larger proportion of patients who were previously non–transfusion independent became transfusion independent over any 12-week period in the pacritinib arms compared with the control arm, Rampal adds. Specifically, 27% and 25% of patients treated with 200-mg or 400-mg doses of pacritinib, respectively, achieved transfusion independence, compared with 5% of patients who were given BAT.

Funding supported by CTI BioPharma. Content independently developed by OncLive.