Background: In patients with myelofibrosis (MF), JAK inhibitor therapy can improve both splenomegaly and disease symptoms. Unfortunately, dosing – and thus efficacy – of available current JAK1/2 inhibitors is frequently limited in patients with cytopenic MF due to drug-induced exacerbation of cytopenias. Pacritinib is a novel JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 that has been studied at full dose in patients with MF regardless of cytopenias. Here, we present data on spleen and symptom benefit in pacritinib-treated patients across the cytopenic spectrum, stratified by both baseline platelet (PLT) count and hemoglobin (HB) level. Methods: Evaluable patients treated with pacritinib in the PERSIST-1 and PERSIST-2 studies were analyzed, stratified by baseline PLT (<100, ≥100x10⁹/L) and HB (<8, 8 to <10, ≥10 g/dL). Groups were analyzed for depth of spleen volume response (SVR), modified total symptom score (TSS) response, patient global impression of change (PGIC), and dose intensity. Results: Of 276 patients evaluable for spleen response, median age was 67 years, 51.5% had grade 3 fibrosis, 70% had primary MF, and 16% had prior JAK2 inhibitor exposure. Median dose intensity was >99.7% for the duration of the study across PLT and HB subgroups. Overall, 80% of patients had ≥10% SVR (SVR-10), 75.5% had TSS-10, and 78% reported that their symptoms were improved at week 24. Week 24 spleen reduction occurred consistently across PLT and HB strata, with 84-93% and 86-90% of patients respectively (Table). SVR-35 occurred in 23-25% of patients across PLT strata and in 21-28% of patients across HB strata. Symptom response was also consistent across strata, though TSS-50 occurred at highest rates (62.5%) in patients with HB <8 g/dL. There was no diminution in symptom burden reduction in patients with thrombocytopenia (Table). Across all subgroups, at least three-quarters of patients reported symptoms were “improved” at week 24. Conclusions: Pacritinib demonstrates consistent efficacy for spleen and symptom response in patients with MF regardless of blood counts. This consistent effect may be related to pacritinib’s unique kinome profile and its ability to be delivered at full dose in patients regardless of cytopenias. Clinical trial information: NCT01773187, NCT02055781.

^aOnly scores from TSS v2.0 were included in this analysis. Abbreviations: HG, hemoglobin; PGIC, patient global impression of change; PLT, platelets; SVR, spleen volume response; TSS, modified total symptom score.