C099 | IMPROVED METABOLIC PROFILE IN PACRITINIB-TREATED PATIENTS WITH MYELOFIBROSIS: A POOLED ANALYSIS OF PROSPECTIVE CLINICAL TRIALS

Background: Serum albumin is a prognostic marker in patients with myelofibrosis (MF), with levels <4.3 g/dL associated with inferior survival [Tefferi A, et al. Blood Adv. 2018]. Retrospective data suggest that ruxolitinib is associated with increases in albumin [Kuykendall AT, et al. JCO Precision Oncology, 2024], as well as weight gain and cholesterol levels, which may be bothersome or may impact cardiovascular risk. The metabolic profile of the JAK2/IRAK1/ACVR1 inhibitor pacritinib (PAC) has not previously been described. Methods: Patients with MF who were treated with PAC (400mg total daily dose) in PERSIST-1 (NCT01773187), PERSIST-2 (NCT02055781), and PAC203 (NCT04884191) were included. Shifts from baseline in albumin, weight, body mass index (BMI) and metformin/insulin use were analyzed over a 24 week follow-up. Results: A total of 484 PAC-treated patients were included. At baseline (BL), median age was 68 years, 56% were male, median values: weight 71 kg; BMI 24.5 kg/m² (BMI<20: 7%, normal: 48%, >25: 42%) albumin 4.20 g/dL; hemoglobin 9.8 g/dL; platelets 80 x10⁹/L, and the median total cholesterol was 2.95 mmol/L. Among patients with BL hypoalbuminemia (<3.5 g/dL), 65% (11/17) had improvement to normal albumin levels at Week 12, and 18% (3/17) had values ≥4.3 g/dL. Among patients with BL intermediate albumin values (3.5 to <4.3 g/dL), 44% (93/210) improved to ≥4.3 g/dL whereas only 6% (12/210) developed hypoalbuminemia. Among patients starting with higher albumin values, 87% (171/197) maintained values ≥4.3 g/dL. Similar trends were observed among patients at Week 24, with 73% (8/11) of patients with BL hypoalbuminemia improving to normal levels, 41% (64/156) with BL intermediate values improving values ≥4.3 g/dL, and 85% (144/170) with BL values ≥4.3 g/dL maintaining these levels (Figure). Over this interval, weight remained stable, with median change 0 kg (IQR: -1.3, +1.8 kg) at Week 12 and +0.3 kg (IQR: -1.3, +3.14 kg) at Week 24. Among 26 patients requiring metformin at study start, 19% (n=5) discontinued metformin while on PAC. Among 15 patients requiring insulin at study start, 1 discontinued insulin on study treatment. Conclusions: Patients with MF treated with PAC trend towards improvement in serum albumin while maintaining stable weight in this post-hoc analysis. Further analysis is warranted to confirm these findings and assess other metabolic effects. © American Society of Hematology (2024). Reused with permission