The final safety and efficacy results from a ruxolitinib dose-finding study of patients with myelofibrosis (MF) and low platelet counts support the use of ruxolitinib 10 mg twice daily in these patients.
The research was conducted because “thrombocytopenia is a common feature of MF, a myeloproliferative neoplasm driven by dysregulated JAK/STAT signaling; however, pivotal trials assessing the efficacy of ruxolitinib (a JAK1/2 inhibitor) excluded patients [with MF] with low platelet counts,” study author Paola Guglielmelli, MD, PhD, of the University of Florence, and colleagues wrote.
The open-label, dose-finding, phase Ib EXPAND study included 69 patients with MF, 38 of whom received ruxolitinib at the maximum safe starting dose and were the focus of the analysis. The researchers stratified patients by their baseline platelet count, with patients who had baseline platelet counts of 75 to <100 × 109/L comprising one group (n=20) and those with baseline platelet counts of 50 to <75 × 109/L (n=18) comprising a second group.
Patients in both groups garnered “substantial clinical benefits” from the treatment, Dr. Guglielmelli and colleagues wrote. Half of the patients with baseline platelet counts of 75 to <100 × 109/L achieved a spleen response, defined as a >50% reduction in spleen length from baseline, while 67% of the patients with baseline platelet counts of 50 to <75 × 109/L achieved a spleen response.
There were no “new or unexpected safety signals,” and the “incidence of adverse events was consistent with the known safety profile of ruxolitinib,” according to the investigators.
Thrombocytopenia and anemia were the most common adverse events. Thrombocytopenia occurred in half of the patients with baseline platelet counts of 75 to <100 × 109/L and in 78% of patients with baseline platelet counts of 50 to <75 × 109/L. Anemia occurred in 55% and 44% of patients, respectively.
“Overall, the safety profile of a 10 mg [twice daily] dose of ruxolitinib in this study was acceptable and consistent with the known overall safety profile of ruxolitinib in patients with MF,” Dr. Guglielmelli and colleagues concluded. “Treatment at this dose improved symptoms in these patients, even in those at a more advanced stage of disease. Results from this long-term study support the use of 10 mg [twice daily] as the maximum recommended starting dose of ruxolitinib in patients with low platelet counts.”
Guglielmelli P, Kiladjian JJ, Vannucchi AM, et al. Efficacy and safety of ruxolitinib in patients with myelofibrosis and low platelet count (50 × 109/L to <100 × 109/L) at baseline: the final analysis of EXPAND. Ther Adv Hematol. 2022. doi:10.1177/20406207221118429