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Pacritinib demonstrates safety, efficacy for patients with myelofibrosis
Pacritinib safely improved disease-related symptoms and reduced spleen volume in patients with myelofibrosis who had pre-existing anemia and thrombocytopenia, according to phase 2 study results.
“Currently, myelofibrosis patients with anemia and thrombocytopenia have limited treatment options for splenomegaly and constitutional symptoms and these data show that pacritinib has potential to help patients who are sub-optimally managed on currently available treatments,” Rami S. Komrokji, MD, associate professor of oncologic sciences at the University of South Florida College of Medicine and clinical director of the department of malignant hematology at Moffitt Cancer Center, said in a press release.
Komrokji and colleagues conducted a multi-center study to evaluate the efficacy and safety of pacritinib (CTI Biopharma) — a JAK2 and FLT3 kinase inhibitor which previously has shown promise in phase 1 studies — in patients with myelofibrosis.
The analysis included 35 patients (median age, 69 years) with myelofibrosis who had clinical splenomegaly that could not be controlled through standard therapy or who were newly diagnosed with intermediate or high-risk disease. These patients were eligible with any degree of thrombocytopenia, anemia or neutropenia.
At baseline, 40% of the patients had hemoglobin levels lower than 10 g/dl and 43% had platelets less than 100,000/microliter.
Patients received 400 mg pacritinib daily in 28-day cycles.
Spleen response rate — or the proportion of patients who achieved at least a 35% reduction in spleen volume from baseline through week 24 measured by MRI — served as the primary endpoint. Secondary endpoints included a 50% or greater reduction in spleen size by physical exam and a 50% reduction in total symptom score measured with the Myelofibrosis Symptom Assessment Form by week 24.
Overall, 31% of patients achieved at least a 35% reduction in spleen volume from baseline to week 24, and 42% of patients had a maximum reduction in spleen length below the costal margin of at least 50%.
Fifteen patients (48.4%) achieved at least a 50% reduction in total symptom score, which represented improvements in abdominal pain, bone pain, early satiety, fatigue, inactivity, night sweats and pruritus. The median myelofibrosis symptom improvement was at least 50% for all symptoms except fatigue.
Grade 1 and grade 2 diarrhea (69%) and nausea (46%) were the most common adverse events associated with pacritinib. Treatment discontinuation occurred in 26% of the patients due to adverse events, four of which were considered severe. Serious adverse events related to pacritinib included febrile neutropenia, thrombocytopenia, myocardial infarction, hyperbilirubinemia, hypersensitivity, septic shock, subdural hematoma, supratherapeutic international normalized ratio in a patient anticoagulated with warfarin, dehydration, hyperuricemia and hyponatremia (n = 1 for all).
“Pacritinib is an active and well-tolerated agent for treatment of myelofibrosis with manageable gastrointestinal toxicity and minimal myelosuppression compared to ruxolitinib [Jakafi, Incyte],” the researchers wrote. “Pacritinib may provide a therapeutic option for myelofibrosis patients with baseline cytopenias and is currently being evaluated in two phase 3 trials.” – by Anthony SanFilippo
Disclosure: Komrokji reports no relevant financial disclosures. The other researchers report consultant/advisory roles and employment with and honoraria and research funding from CTI Biopharma. They report additional financial relationships with Celgene, Genentech, Gilead, Incyte, Lilly, NS Pharma, Promedior, Sanofi and S*Bio Pte.