BET inhibitors combined with JAK inhibitors well-tolerated with myelofibrosis
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SAN DIEGO — The BET inhibitor BMS986158 has continued to be well tolerated in combination with ruxolitinib and fedratinib in patients with intermediate- or high-risk myelofibrosis, according to a study presented at ASH Annual Meeting.
The phase 1/phase 2 CA011-023 study has so far produced “promising preliminary data of potential disease modification,” according to a primarily European research team headed by Haifa Kathrin Al-Ali, MD, head of the Krukenberg Cancer Center at University Hospital of Halle in Germany.
BMS-986158, an “orally bioavailable, potent, and selective” BET inhibitor, has shown in previous studies to be well tolerated as a first-line treatment in combination with ruxolitinib (Jakafi, Incyte) and as a second-line treatment in combination with fedratinib (Inrebic, Bristol Myers Squibb), another example of BET inhibitors and JAK inhibitors working well together in myelofibrosis treatment.
This set of data from the phase 1/2 CA011-023 study examined 16 patients with myelofibrosis receiving BMS-986158 with ruxolitinib as a first-line treatment, and 24 patients receiving the BET inhibitor with fedratinib as a second-line treatment, both receiving dose escalations.
The study noted “early and deep” spleen volume reduction in both sets of patients, with most patients remaining on treatment at the time of reporting. Al-Ali reported that any treatment related adverse effects were “mostly low-grade and transient,” with thrombocytopenia specifically appearing in only manageable levels.
The study is currently ongoing, with patients currently enrolling in dose expansions for the first-line treatment with ruxolitinib.
Reference:
Lavie D, et al. BMS-986158, a potent BET Inhibitor, in combination with ruxolitinib or fedratinib in patients (pts) with intermediate- or high-risk myelofibrosis (MF): Updated results from a phase 1/2 study. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2023; San Diego.
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