Background: The co-occurrence of thrombocytopenia and anemia (bicytopenia) in patients (pts) with myelofibrosis (MF) is a therapeutic challenge due to treatment-related myelosuppression from JAK2 inhibitors that also target JAK1. Pacritinib (PAC) is a JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 that can be given at full dose, with consistent efficacy regardless of platelet (PLT) count or hemoglobin (Hb) levels. In PERSIST-2, PAC was associated with spleen volume reduction, symptom benefit, and reduced transfusions in pts with bicytopenia. The current study evaluated real-world treatment patterns and outcomes in pts with MF presenting with bicytopenia at the time of PAC initiation.

Methods: This was a US-based multicenter chart-review of pts with MF who initiated treatment with PAC from 06/02/2022 to 07/02/2024. This analysis was on pts with PLT <100 x 109/L and Hb <10.0 g/dL at PAC initiation (index) who were followed to death, end of data availability, or end of the study period (01/22/2025). Pt demographic and clinical characteristics, 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 and Hb levels, MF-related symptoms, and overall survival (OS) from index to post-index day 180 were described using counts and percentages, medians and interquartile range (IQR), and Kaplan Meier survival probabilities.

Results: Of 169 pts treated with PAC, most had bicytopenia at index (66.3%; 112/169). A majority of pts with bicytopenia were male (62%, 69/112) with a median (IQR) age at MF diagnosis of 72 years (65.5, 75.5) and a medina of 4.4 months (0.7, 14.7) from diagnosis to index. Most pts received PAC ast the first JAK inhibitors (55.4%; 62/112) while 44.6% (50/112) received ruxolitinib (n=49) or fedratinib (n=1) prior to PAC. The median follow-up from index was 8.9 months (6.9, 12) and a majority were still on PAC at the end of the 180-day observation period (70.5%; 79/112). At index, median PLT count was 44.5 x 109/L (40, 48) and a majority of pts (81%; 91/112) had severe thrombocytopenia (PLT <50 x 109/L). Median Hb level at index was 8.5 g/dL (8.0, 9.0) and 82% of pts had moderate anemia (Hb ≥8 g/dL to <10g/dL).

Of the 53 pts with spleen assessment at index and day 180, 25 (47%) pts had a reduction in spleen size by at least 1 category by day 180. Of those with a response, 15 pts had severe splenomegaly at index with 14 (93.3%) pts achieving a reduction to moderate and 1 pt to mild. Of the 8 pts with moderate splenomegaly at index, 7 (87.5%) pts had a reduction to mild and 1 pt achieved reduction to NP. Lastly, 2 pt with mild splenomegaly at index achieved a reduction to NP. The remaining 28 pts did not see a categorical change or worsening in spleen size.

Many pts (97%; 109/112) reported ≥1 MF-related symptom at index, with fatigue (91%; 99/109) and abdominal discomfort (58%; 63/109) being most common. Early symptom improvement was experienced by 51% of pts (56/109) reporting a decrease in the number of symptoms at any time up to day 30 with a 20% reduction (IQR: 0.0%, 50%) in the median number of symptoms from index to day 30 (n=109). Symptom improvement continued with 83% of pts (91/109) reporting a decrease in symptoms at the most recent assessment up to day 180 with a 67% reduction (IQR: 50%, 100%) in the median number of symptoms from index to day 180 (n=109).

At day 180, median PLT count increased by 37.5% (IQR: 19%, 90%) (n=92) and 31% (34/109) of pts achieved an IWG-PLT response with an absolute increase in PLT ≥30 x 109/L. From index to day 180, Hb levels increased by a median of 0.8 (IQR: 0.0, 1.10) (n=92). During the observation period, 28.5% of pts achieved ≥1.0 g/dL increase in Hb from index and 17% (19/112) achieved ≥1.5 g/dL increase.

By the end of the observation period, 82% (92/112) of pts were alive and 6-month OS probability was 92% (95% CI: 85.1-95.7).

Conclusions: Pts with MF who have both thrombocytopenia and anemia, treated with PAC in the real-world, experienced reduction or stabilization in spleen size category, along with improvements in MF-related symtpom burder, PLT and Hb. A majority of PAC treated pts experiecned symptom relief with benefits observed as early as 30 days following treatment initiation. PAC may have clinical utility in addressing unmet needs of pts with MF who have bicytopenias.

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2025
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