PracticeUpdate: Conference Series - EHA 2018

Use of Ruxolitinib–Hydroxyurea Benefits Patients with Myelofibrosis Addition of hydroxyurea could improve hematological control, disease-related symptoms, and splenomegaly T here is a clinical and hematological benefit to the combined use of rux- olitinib and hydroxyurea in patients

with myelofibrosis (MF). Furthermore, the drug combination appears to be safe, with no cumulative or overlapping toxicities, as reported in study results presented at EHA 2018. The addition of hydroxyurea could improve hematological control, disease-related symptoms, and splenomegaly in cases where ruxolitinib resistance, with regard to white blood cells and platelet counts, is documented in the hyperproliferative phase of MF, the research team, led by Novella Pugliese, MD, with the University of Naples Federico II in Italy, stated in their abstract. Ruxolitinib, an oral JAK1 and JAK2 inhibitor, is the first drug approved for the treat- ment of MF, a progressive, potentially life-threatening blood cancer with limited treatment options. The drug received approval from the US Food and Drug Administration in 2011 for the treatment of patients with intermediate or high-risk myelofibrosis, which represents up to 90% of all MF patients. The following year the European Union approved use of the drug for patients with this disease. Although ruxolitinib has been shown to significantly reduce splenomegaly and disease-related symptoms, no clear sur- vival benefit has been demonstrated. This may reflect suboptimal drug exposure related to the lower dosages needed to minimize hematological toxicity, specifi- cally cytopenias, the researchers stated in their abstract. “Furthermore,” they noted, “the optimal management of spe- cific conditions such as leukocytosis or thrombocytosis is still undefined.” The investigators hypothesized that treating MF patients with ruxolitinib in combination with a cytoreductive agent like hydroxyurea might improve hema- tological response. Their observational multi-center study analyzed 20 adult patients with a diagnosis of intermediate or high-risk primary MF, post-polycythemia vera MF, or post-essential thrombo- cythemia MF requiring the addition of hydroxyurea to ruxolitinib treatment to

treatment, the investigators stated. However, 2 patients temporarily reduced ruxolitinib treatment during the co-admin- istration period and one discontinued the drug altogether due to severe thrombo- cytopenia. In addition, 8 patients reduced hydroxyurea due to hematological toxicity that occurred primarily in the first 8 to 12 weeks of treatment. A symptomatic response was obtained in 6 patients during ruxolitinib monotherapy and in 12 patients during combination rux- olitinib-hydroxyurea. A spleen response was obtained in 5 patients during ruxol- itinib monotherapy and 8 patients with combination therapy. After a median duration of 14.5 months of combination therapy, 16/20 patients had a hematological response; 14/17 patients who had started combination therapy to control white blood cell count and 2/3 who started in order to reduce platelets count. “The number of patients requiring ruxolitinib dosage reduction or discontinuations was lower during com- bination therapy, and ruxolitinib dosage was increased in 50% of patients,” the researchers stated in their abstract.

control white blood cell or platelet count. Ruxolitinib was initially given at a dose of 5, 15, or 20 mg twice daily, depend- ing on baseline platelet count, adjusted in response to platelet/neutrophil count and/or lack of efficacy. Hydroxyurea was added when white blood cell or plate- let counts were unsatisfactory. Patient response was evaluated based on four criteria – spleen size, symptoms, white blood cell and platelets count – asset out in response criteria developed by the European LeukemiaNet. All patients received ruxolitinib as a sin- gle therapy after a median time from MF diagnosis of 15.9 months (range 1.6–181 months). The starting dose of ruxolitinib as monotherapy was 20 mg BID in 40% of cases, 15 mg BID in 35%, 10 mg BID in 5%, and 5 mg BID for the 20%. In total, 17 patients started hydroxyurea treatment as a result of insufficient white blood cell control and 3 patients because of unsatis- factory platelet control. Hydroxyurea was added after a median time of ruxolitinib monotherapy of 6.5 months (range 1–49.6 months). The median time of combination therapy was 14.5 months (range 2–195). Toxicity was generally manageable with dose reductions and/or supportive

www.practiceupdate.com/c/69938

EHA 2018 • PRACTICEUPDATE CONFERENCE SERIES 13