P1068: RISK-ADJUSTED SAFETY ANALYSIS OF PACRITINIB IN PATIENTS WITH MYELOFIBROSIS

Abstract

Background: Pacritinib is a novel JAK2/IRAK1 inhibitor that has shown clinically significant activity in patients with myelofibrosis, including those with platelet counts <50 x 109/L. Recently, JAK inhibitors have come under increased scrutiny due to specific, emerging toxicities with drugs in this class. Aims: This safety analysis focuses on these toxicities of interest for patients treated with pacritinib 200 mg twice daily (BID) and best available therapy (BAT), including ruxolitinib, on the phase 3 PERSIST-2 and phase 2 PAC203 studies. Data are presented as risk-adjusted incidences to account for differential time at risk for adverse events (AEs) between arms due to cross-over. Methods: Patients treated with pacritinib 200 mg BID on PERSIST-2 and PAC203, and those treated with BAT, including ruxolitinib on PERSIST-2, were included. Risk-adjusted AEs, representing event rate per 100 patient-years, were calculated for the following: overall and fatal AEs, bleeding AEs (determined by Standardized Medical Dictionary for Regulatory Activities Query [SMQ]), cardiac AEs (by SMQ), major cardiac events (determined by major adverse cardiovascular events [MACE] classification), infections, thromboses, and secondary malignancies. Results: A total of 160 patients were analyzed as the pooled pacritinib 200 mg BID group (n=106 in PERSIST-2; n=54 in PAC203) and 98 patients in the BAT group (44 on ruxolitinib). At baseline, the median platelet count was 57 x 109/L for the pooled pacritinib group and BAT group; hemoglobin was 9.2 vs 9.7 g/dL and 66% vs 53% had prior JAK2 inhibitor therapy respectively. The rate of AEs was higher on pacritinib versus BAT, while the rate of fatal AEs was lower (Table 1). Both bleeding and cardiac events occurred at slightly lower rates on pacritinib compared to BAT. There were no MACE for pacritinib, whereas there were for BAT, including in patients treated with ruxolitinib. Malignant neoplasms (excluding worsening myelofibrosis and leukemia) occurred at similar rates on pacritinib and BAT, though rate of non-melanoma skin cancers was lower in the pooled pacritinib group (3/100 patient-years) versus BAT (7/100 patient-years), including ruxolitinib (11/100 patient-years). Infection occurred more frequently on pacritinib versus BAT, though fungal and viral infections occurred less frequently, as did Herpes Zoster reactivation (pooled pacritinib: 0/100 patient-years vs BAT: 2.4/100 patient-years, including ruxolitinib: 5.5/100 patient-years). Thrombosis occurred at similar rates on pacritinib and BAT. Image:Summary/Conclusion: Risk-adjusted analysis demonstrates that the safety profile of pacritinib 200 mg BID is comparable or superior to BAT, including ruxolitinib. Pacritinib 200 mg BID may represent a full-dose therapeutic option for patients with myelofibrosis, including those with thrombocytopenia.