MPN-141 Retrospective Comparison of Patient Outcomes on Pacritinib Versus Ruxolitinib in Patients With Myelofibrosis and Thrombocytopenia

Background: Pacritinib (PAC) is a JAK2/IRAK1 inhibitor for patients with myelofibrosis (MF) and thrombocytopenia. Unlike the JAK1/2 inhibitor ruxolitinib (RUX), which is used at lower doses in patients with thrombocytopenia, PAC has been studied at full dose regardless of platelet count. Methods: This analysis focused on PERSIST-2 patients with platelet counts ≤100 × 10⁹/L who were randomized to PAC 200mg BID and patients who received RUX on best available therapy (BAT) prior to week 24. Endpoints included percent of patients with 35% spleen volume reduction (SVR), 50% modified total symptom score (mTSS) reduction (based on early satiety, abdominal discomfort, night sweats, itching, bone pain, and rib pain), and improvement in disease symptoms measured by Patient Global Impression of Change (PGIC). Safety analyses were based on all treated patients; efficacy analyses were based on the intention-to-treat population randomized at least 22 weeks prior to study end. The Fisher Exact test was used to describe differences in response. Logistic and Cox regression was used to adjust for differences in baseline characteristics. Results: Safety analysis included 106 patients on PAC and 44 on RUX; efficacy analysis included 74 on PAC and 32 on RUX (median total daily dose 10 mg). Baseline characteristics were similar between groups, including median platelet count (55 vs 61 × 10⁹/L) and percent receiving RBC transfusion (46% vs 43%). Patients treated with PAC vs RUX achieved higher rates of SVR (22% vs 3%, p=0.02) and numerically higher rates of mTSS response (35% vs 19%; p=0.11) and “much” or “very much” improved symptoms (35% vs 16%, p=0.06) at week 24. Among RUX patients with an available PGIC measure at week 24, 50% reported either no improvement or worsening symptoms, while 76% of PAC patients reported improvement. The adjusted hazard ratio on PAC vs RUX was 0.46 [95% CI: 0.15-1.43]. Bleeding occurred at similar rates (43% vs 41%) on PAC vs RUX. Fatal AEs occurred in 8% on PAC compared to 11% on RUX. Conclusions: PAC yielded higher response rates and a similar safety profile to lower-dose RUX in patients with MF who have moderate or severe thrombocytopenia. This study was supported by CTI BioPharma.