John O. Mascarenhas, MD, discusses pacritinib for patients with myelofibrosis and thrombocytopenia.
John O. Mascarenhas, MD, associate professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai, director of the Adult Leukemia Program, and leader of Clinical Investigation within the Myeloproliferative Disorders Program at Mount Sinai, discusses pacritinib for patients with myelofibrosis and thrombocytopenia.
Mascarenhas thinks pacritinib is an important drug and potentially an agent that will be available in the commercial space because it's the only JAK2 inhibitor that appears to have the least amount of myelosuppression, especially with thrombocytopenia, of the many that have been evaluated. There is an unmet need for patients with extreme thrombocytopenia, defined as platelet counts less than 50,000. Physicians can't effectively and safely deliver the currently approved JAK inhibitors, and there are limited therapies for these patients. He says these patients are typified by a myelodepleted phenotype, so they don't always have large spleens, but they usually are characterized by low blood counts and poor outcomes.
The PERSIST-2 study, a randomized phase 3 study, had efficacy with pacritinib at 20 mg twice a day in both spleen and symptom improvement in these patients with low platelet. The PAC203 was a dose-finding phase 2 randomized study looking at 3 different dose levels, 200 mg twice daily, 100 mg twice daily, and 100 mg once daily. The importance of that study was to document and confirm that the drug can be delivered safely, according to Mascarenhas. The 200 mg twice daily was effective in about 17% of patients in achieving spleen volume reduction, without incurring significant thrombocytopenia. The niche for pacritinib is patients with myelofibrosis who have less than 180 days of prior JAK2 inhibitor therapy that have a platelet count below 50,000.
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