Results of a Phase 2 Study of Pacritinib (SB1518), a Novel Oral JAK2 Inhibitor, In Patients with Primary, Post-Polycythemia Vera, and Post-Essential Thrombocythemia Myelofibrosis

Thirty-four MF patients (median age 69; range, 44–84 years) consented and were enrolled, of which 25 (74%) were men. Median PS was 1 with 2 patients having PS >1. Median baseline hemoglobin and platelet count were 10.2 g/dL and 119,000/μL, respectively. Fifteen patients (44%) had platelet counts <100,000/μL, including 7 with counts <50,000/μL. Median baseline spleen size was 14 cm (range 4–30 cm) below the LCM by physical exam, and median spleen volume was 2647 cc (range 404–7817 cc) by MRI. Twenty-six patients (76%) were JAK2^V617F mutation-positive. The median time on study is 8.2 months (range, 0.5 to 12.1 months).

Seventeen patients (50%) have discontinued, including 8 (24%) due to AEs (1 each for nausea, sepsis, increased bilirubin, subdural hematoma, allergic reaction, GI bleed, and 2 due to thrombocytopenia), 5 for disease progression and 2 for lack of response. Of the AEs leading to discontinuation, only increased bilirubin, allergic reaction and intermittent nausea were considered possibly drug related. Ten patients required dose reduction for adverse events. One patient required drug discontinuation associated with decreased neutrophils and platelets. This was considered related to worsening disease; otherwise, there were no changes in pacritinib dosing related to impaired hematopoiesis. The most common treatment-related AEs were gastrointestinal, which were generally low grade and easily managed. GI AEs >Grade 2 included Grade 3 diarrhea in 2 patients (6%). Only 1 patient discontinued for GI toxicity.

Pacritinib produced meaningful reductions in splenomegaly. Thirty patients (88%) showed reductions in palpable splenomegaly; 15 (44%) showed decreases of ≥50% and 6 (18%) achieved clinical resolution of splenomegaly. Eleven patients (32%) had a ≥35% reduction in splenic volume as measured by MRI. Splenic reduction of 50% by PE correlated with a 25% reduction in spleen volume by MRI. Fourteen patients (41%) had reduction in splenic volume by >25%. Spleen response rates were equivalent among patients with low baseline platelet counts and those with normal baseline counts. All spleen responses are ongoing; consequently a median duration of response has not been reached. Two patients met IWG-MRT criteria for clinical improvement in hemoglobin including 1 who became transfusion independent. At the 6-month visit, a significant reduction (>2 point improvement) was observed for MF-associated symptoms, including abdominal pain, bone pain, early satiety, worst fatigue, inactivity, night sweats and pruritus.