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Abstract Background: Ruxolitinib (RUX) is a JAK1/2 inhibitor known to induce myelosuppression and is often used at suboptimal doses in patients (pts) with cytopenic myelofibrosis (MF) due to concerns of, or in response to treatment-related cytopenia. Unlike RUX, pacritinib (PAC) is a JAK1 sparing JAK2/IRAK1/ACVR1 inhibitor that can be used at full dose regardless of platelet (PLT) count. The objective of this study is to evaluate real-world treatment patterns and outcomes in patients (pts) with MF treated with PAC following a switch from RUX. Methods: This was a US-based multicenter chart-review (85% community) of pts with MF starting treatment with PAC from 06/02/2022 to 07/02/2024. For the pts treated with RUX prior to PAC, treatment patterns, spleen size category (based on palpation or ultrasound: not palpable [NP], including minimally palpable <5 cm below costal margin; mild: 5-10 cm palpable; moderate: 11-20 cm palpable; and severe: >20 cm palpable), PLT counts, hemoglobin (Hb) levels, symptoms, and overall survival (OS) were assessed from PAC initiation (index) through the earliest event of: death, end of data availability, or end of the study period (01/22/2025). Continuous variables were summarized using medians, and interquartile range (IQR), and categorical variables were reported as counts and percentages. Kaplan Meier survival probabilities and 95% confidence intervals (CI) were estimated. Results: Of 169 pts with MF treated with PAC, 36% (61/169) received PAC following RUX – a majority of whom were male (65.5%), White (80.3%), with a median age at MF diagnosis of 70 years (IQR: 64, 75), and a median time from MF diagnosis to PAC initiation of 14.7 months (IQR: 10.0, 28.4). Prior to PAC-initiation, 32.7% of pts (20/61) had ≥1 dose reduction while on RUX – adverse events (65%; 13/20) and intolerability (40%; 8/20) were the most common reasons for RUX dose reduction. Of the 27 pts with spleen assessment at index and day 180, 11 pts (40.7%) had reduction in spleen size by 1 category. Of those with a response, all 9 pts with severe splenomegaly at index achieved a reduction to moderate splenomegaly at day 180. Additionally, 1 pt with moderate splenomegaly at index achieved a reduction to mild by day 180 and 1 pt with mild splenomegaly at index achieved a reduction to NP by day 180. The remaining 16 pts did not see a worsening in spleen size. At index, 95% of pts (58/61) had ≥1 MF-related symptom. Symptom improvement was experienced by 70% (40/58) pts reporting a decrease in the number of symptoms at any time up to day 90 with a 37% reduction (IQR: 0.0%, 66.7%) in the median number of symptoms from index to day 90 (n=58). Symptom improvement continued with 81% of pts (47/58) reporting a decrease in symptoms at any time up to day 180 with a 67% reduction (IQR: 50%, 100%) in the median number of symptoms from index to day 180 (n=58). At index, the median PLT count was 45 x109/L (IQR: 40, 55) with 66.7% (n=40) and 25% (n=15) having severe (PLT <50 x109/L) and moderate (PLT ≥50 to <100 x109/L) thrombocytopenia at index respectively. Of pts with PLT at index and day 180 (n=49), a median increase of 37.7% (IQR: 22.2%, 66.7%) was noted. Among 52 pts with PLT >20 to <100 x 109/L at index, 35% (18/52) achieved an IWG PLT response with an absolute increase ≥30 x109/L. Median Hb was 8.5 g/dL (IQR: 8.0, 9.2) at index and most pts had Hb <10 g/dL (90%; 54/60). Hb increased by a median of 0.8 g/dL (IQR: 0.0, 1.0) from index through day 180 (n=49). By day 180, 29.5% (13/44) of pts with Hb <10 g/dL at index achieved >1.0 g/dL increase in Hb, and 13.3% (6/45) achieved ≥1.5 g/dL increase. OS through the end of the study period was 80.3% (49/61), and 6-month OS probability was 88.5% (95% CI: 77.4-94.4). Conclusion: This real-world study demonstrated the utility of switching to PAC following RUX treatment. A majority of pts had thrombocytopenia or anemia at the time of PAC initiation with most pts experiencing symptom relief during PAC treatment, clinically meaningful benefits in spleen size and improvement in PLT and Hb following PAC treatment.