Researchers Present Early Data on BET Inhibitor BMS-986158 in Myelofibrosis

BMS-986158 combined with ruxolitinib or fedratinib reduced spleen volume in patients with myelofibrosis (MF), according to study results presented at the 2022 American Society of Hematology (ASH) Annual Meeting. The study also found that adverse events were mostly grade 1 or 2 and that grade 3 adverse events could be successfully managed with dose delays or modifications.

BMS-986158 is an inhibitor of bromodomain and extraterminal (BET) proteins, which have been found to be involved in the proliferation and survival of cancer cells. Therefore, BET inhibition is a new potential therapeutic approach, either alone or in combination with Janus kinase (JAK) inhibitors such as ruxolitinib and fedratinib.

The authors, led by Rosa Ayala, of the Hematology and Hemotherapy Department at University Hospital in Madrid, Spain, presented initial safety and efficacy data from the dose-escalation portion of study. The analysis presented at ASH included 13 patients with either primary or secondary MF and splenomegaly who were treated by May 31, 2022. Six patients received BMS-986158 plus ruxolitinib, and seven received BMS-986158 plus fedratinib.

Grade 1/2 adverse events occurred in three patients in the BMS-986158 plus ruxolitinib group and two patients in the BMS-986158 plus fedratinib group. Grade 3 adverse events occurred in four patients in the BMS-986158 plus ruxolitinib group; those were thrombocytopenia (n=2, including one case that required dose limitation), neutropenia (n=1), and hypertension (n=1). Grade 3 adverse events also occurred in three patients in the BMS-986158 plus fedratinib group: anemia (n=2) and thrombocytopenia (n=1). No grade 4/5 adverse events occurred in either group, and no treatment discontinuations were necessary.

The researchers also noted that the treatment combination reduced spleen volume in all evaluable patients at week 12. That effect continued into week 24.

The researchers are continuing to analyze JAK2 variant allele frequency in that cohort. In addition, the study is now enrolling patients in the dose-escalation phase of the study, which will aim to establish a recommended dose for phase II.

Reference

Ayala R, Lopez N, Abulafia AS, et al. BMS-986158, a potent BET inhibitor, as monotherapy and in combination with ruxolitinib or fedratinib in intermediate- or high-risk myelofibrosis: first results from a phase 1/2 study. Abstract #4346. Presented at the 64th American Society of Hematology Annual Meeting, December 10-13, 2022; New Orleans, Louisiana.