Abstract Background Pacritinib (PAC), a JAK1-sparing JAK2/IRAK1/ACVR1 inhibitor approved for patients (pts) with myelofibrosis (MF) and severe thrombocytopenia (platelet PLT 50 x109/L) has demonstrated meaningful spleen volume reduction and symptom improvement in clinical trials regardless of PLT count. This study aimed to assess real-world treatment patterns and outcomes in pts with MF treated with PAC in predominantly community settings in the United States. Methods This US-based multicenter chart review study included pts with intermediate- or high-risk primary or secondary MF who initiated treatment with PAC as first JAKi (1L) or second JAKi (2L) between 06/02/2022, and 07/02/2024. Eligible pts ≥18 years of age at PAC initiation, received PAC for ≥1 month, and had ≥6 months of follow-up from PAC initiation unless deceased during that period. Pts were followed from index until the earliest of death, end of data availability, or end of study period (01/22/2025). Pt characteristics, treatment patterns, change in spleen size category (based on palpation or ultrasound): not palpable NP, including minimally palpable 5cm below costal margin; mild: 5-10cm palpable; moderate: 11-20cm palpable; and severe: 20cm palpable), hematologic outcomes (PLT and hemoglobin Hb), MF-related symptoms, and overall survival from index to post-index Day 180 were reported. Index data were collected ≤14 days prior to or on the PAC initiation date. Results were described using counts and percentages, medians and interquartile range (IQR), and Kaplan Meier survival probabilities. Results A total of 169 pt charts were abstracted (61.5% 1L; 38.5% 2L). Median age at MF diagnosis was 71 years (IQR: 65.0-76.0); 58.6% male and 72.2% White. Prior to PAC initiation, most 2L pts (93.8%, 61/65) received ruxolitinib. The median (IQR) time from MF diagnosis to index was 2.5 months (IQR: 0.8-13.9) and median duration of follow-up from PAC initiation was 9.2 (IQR: 6.8–13.2) months. There were 73.4% of pts still on PAC at the end of follow-up. Of 68 pts with spleen data at index and Day 180, 31(45.6%) achieved a reduction in spleen size category. Of 8 pts with mild splenomegaly, 5 (62.5%) became NP. Of 41 pts with moderate splenomegaly, 10 (24.4%) achieved a reduction in spleen size category (NP: n=1; mild: n=9). Of 19 pts with severe splenomegaly, 16 (84.2%) achieved a reduction in spleen size category (mild: n=1; moderate: n=15). The remaining 37 pts did not see a worsening in spleen size category. At index, the median PLT count was 45.0x109/L (IQR: 40.0-50.0); most pts (91.1%; 153/168) presented with thrombocytopenia (PLT 100x109/L) and 26.8% (45/168) had PLT 50x109/L. Overall, PLT count increased from index to Day 180 by a median (n, IQR) 37.5% (140, 14.8-113.7). By Day 180, 38.0% (57/150) of pts achieved an International Working Group PLT response (absolute increase of ≥30,000/µL during index treatment among those with a pre-index PLT count 20 to ≤100). At index, median Hb was 9.0 g/dL (IQR: 8.1-9.8) and most pts had Hb 10 g/dL (77.3%; 126/163). From index to Day 180, Hb increased by a median (n, IQR) of 0.5 g/dL (135, -0.2-1.0). By Day 180, 34.3% (35/102) and 20.6% (21/102) of pts with index Hb 10 g/dL achieved increases of ≥1.0 g/dL and ≥1.5 g/dLrespectively. At index, 95.9% (162/169) of pts had ≥1 MF-related symptom with fatigue being the most common (84.0%; 136/162). Between Day 180, 82.7% (134/162) of pts experienced a reduction in the number of symptoms, with a median 67% (IQR: 50.0-100) reduction in symptom burden. By the end of the study, 85.8% (145/169) of pts were alive, and the survival probability from PAC initiation to Day 180 was 93.5 (95% confidence interval: 88.6-96.3). Spleen size reduction, PLT and Hb response, symptom reduction and survival outcomes were consistent regardless of whether PAC was used as 1L or 2L JAKi therapy. Conclusion In real-world clinical settings, pts with MF treated with PAC, regardless of the line of therapy, experienced reduction or stabilization in spleen size category, improvement in hematologic parameters, and a diminution of MF symptom burden.
Marrone et al. (Mon,) studied this question.