Study Supports Use of Pelabresib Monotherapy in High-Risk Essential Thrombocythemia

Researchers have suggested that pelabresib, an investigational oral BET inhibitor, provides clinical benefit in patients with high-risk essential thrombocythemia that is refractory or intolerant to hydroxyurea.

The researchers shared preliminary results of an arm of the MANIFEST study, showing hematologic responses and symptom improvement, during the 2023 American Society of Clinical Oncology Annual Meeting.

“High-risk essential thrombocythemia is characterized by thrombocytosis, thrombohemorrhagic events, and systemic symptoms. Patients can experience intolerance, inadequate response, or loss of response to first-line cytoreductive therapies, such as hydroxyurea or interferon alfa-2a,” wrote the authors, led by Francesco Passamonti, MD, of the University of Insubria in Varese, Italy.

The phase II MANIFEST study suggested that pelabresib could be beneficial in myelofibrosis. The current analysis explores the safety and efficacy of the agent as monotherapy in high-risk essential thrombocythemia. At the time of analysis, researchers had enrolled 20 patients with high-risk essential thrombocythemia with platelet counts of more than 600×109/L and two or more symptoms. The median age was 64 years. At baseline, their median hemoglobin was 13 g/dL, median platelet count was 772x 109/L, and median total symptom score was 32.7.

The subjects received 225 mg of pelabresib every day. A large majority of patients (18 of 20; 90%) had a hematologic response, including normalization of platelet count and white blood cell count and normal spleen size. At week 12, the median platelet count was 446×10⁹/L and the median white blood count was 8.2×10⁹/L. Furthermore, 86% of patients had a reduction in total symptom score, and hemoglobin was stable through week 24.

Safety results were consistent with the known safety profile of pelabresib. The most common nonhematologic adverse events were nausea (60%), diarrhea (35%), and dysgeusia (35%). In all, 30% of patients experienced hemorrhagic or thromboembolic events, but none were above grade 3.

Reference

Passamonti F, Patriarca A, Knapper S, et al. Pelabresib (CPI-0610) monotherapy in high-risk essential thrombocythemia refractory or intolerant to hydroxyurea: Preliminary results from MANIFEST study. Abstract #7019. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, Illinois.