Risk-adjusted safety analysis of pacritinib (PAC) in patients (pts) with myelofibrosis (MF)

7058 Background: PAC is a novel JAK2/IRAK1 inhibitor that has shown significant activity in pts with MF, including those with platelet (plt) counts 9/L. Recently, JAK inhibitors have come under increased scrutiny due to specific, emerging toxicities with drugs in this class. This safety analysis focuses on these toxicities of interest for pts treated with PAC 200 mg BID and best available therapy (BAT), including ruxolitinib (RUX), 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: Pts treated with PAC 200 mg BID on PERSIST-2 and PAC203, and those treated with BAT on PERSIST-2, were included. Risk-adjusted AEs, representing event rate per 100 patient-years (pt-yrs), were calculated for overall and fatal AEs, bleeding AEs (determined by Standardized Medical Dictionary for Regulatory Activities Query [SMQ]), cardiac AEs (by SMQ), major cardiac events (per major adverse cardiovascular events [MACE] classification), infections, thromboses, and secondary malignancies. Results: A total of 160 pts were analyzed as the pooled PAC group (n=106 in PERSIST-2; n=54 in PAC203) and 98 pts in the BAT group (44 on RUX). At baseline, median plt count was 57×109/L; 61% had prior JAK2 inhibitor therapy. The rate of AEs was higher on PAC versus BAT, while the rate of fatal AEs was lower (Table). Both bleeding and cardiac events occurred at slightly lower rates on PAC compared to BAT. There were no MACE events on PAC, whereas there were on BAT. Malignant neoplasms occurred at similar rates on PAC and BAT, though rate of non-melanoma skin cancers was lower in pooled PAC (3/100 pt-yrs) versus BAT (7/100 pt-yrs), including RUX (11/100 pt-yrs). Infection occurred more frequently on PAC, though fungal and viral infections occurred less frequently, as did herpes zoster reactivation (pooled PAC: 0/100 pt-yrs vs BAT: 2.4/100 pt-yrs, including RUX: 5.5/100 pt-yrs). Thrombosis occurred at similar rates on PAC and BAT. Conclusions: Risk-adjusted analysis demonstrates that the safety profile of PAC 200 mg BID is comparable or superior to BAT, including RUX. PAC 200 mg BID may represent a full-dose therapeutic option for pts with MF, including those with thrombocytopenia. Clinical trial information: NCT02055781; NCT04884191. [Table: see text]