Treatment with the JAK2 inhibitors pacritinib (Vonjo) and momelotinib (Ojjaara) has shown positive effects on anemia and transfusion requirements in patients with myelofibrosis, according to a real-world study presented at the 2024 ASH Annual Meeting.
The study, conducted at Moffitt Cancer Center, analyzed data from the first 50 patients treated with either pacritinib or momelotinib. The goal was to better understand the hematologic responses, treatment duration, and real-world data associated with these agents after their FDA approvals. Patients receiving momelotinib and pacritinib are typically older with extended disease duration, multiple prior lines of therapy, high-risk mutations, and cytopenia. Pacritinib-treated patients have more prominent baseline thrombocytopenia.
Impact on Anemia and Transfusion Needs
Patients treated with momelotinib (n = 32) experienced an increase in median hemoglobin count from 8.7 g/dL at the start of therapy to 9.0 g/dL after 3 months (P = .021). The median platelet count at the start of therapy was 141 x 109/L and increased to 116 x 109/L after 3 months (P = .317). The mean number of red blood cell (RBC) units required per month decreased from 1.9 to 0.47 after 3 months of treatment (P = .015).
Patients treated with pacritinib (n = 27) had a median hemoglobin count of 8.5 g/dL at the start of treatment, which increased to 9.1 g/dL after 3 months (P = .402). The median platelet count at the start of therapy was 65 x 109/L compared to 31 x 109/L after 3 months (P = .303). The mean number of RBC units required per month decreased from 2.4 to 0.75 after 3 months of therapy (P = .099).
Survival Rates and Discontinuation Reasons
The 6-month overall survival (OS) rates among patients who received momelotinib and pacritinib were 96% and 73%, respectively. The 9-month OS rates were 96% and 64%, respectively (P = .037).
In the momelotinib group, seven patients discontinued therapy due to non-hematologic/gastrointestinal (GI) toxicity, and three discontinued treatment due to thrombocytopenia. In the pacritinib group, seven patients discontinued treatment due to GI toxicity, and six discontinued due to death.
Context of Approvals
Pacritinib received accelerated approval from the FDA in February 2022 for treating adult patients with intermediate or high-risk primary or secondary myelofibrosis with a platelet count below 50,000/µL. Momelotinib was approved by the FDA in September 2023 for treating adult patients with intermediate or high-risk myelofibrosis, including primary or secondary myelofibrosis, and anemia.
Momelotinib Shows Real-World Improvements in Anemia, Symptoms, and Spleen Response
Treatment with momelotinib (Ojjaara) improved anemia and increased rates of transfusion independence (TI) in patients with myelofibrosis; the agent also alleviated symptoms and controlled splenomegaly for those previously exposed to a JAK inhibitor, according to real-world data from a retrospective study presented at the 2024 ASH Annual Meeting.
Among patients who were symptomatic at baseline (n = 126), 92% experienced improvement in disease-related symptoms, including asthenia (76%), anorexia (65%), weight loss (51%), abdominal discomfort (47%), and pruritis (75%). Improvements were sustained at 3-, 6-, 9- and 12-month assessments.
Moreover, the mean hemoglobin level increased from 8.0 g/dL at baseline to 9.3 g/dL at 3 months and was maintained at 9.2 g/dL at 6 months. At 3 months of follow-up, 48.4% of patients who were transfusion dependent (TD) prior to treatment with momelotinib (n = 108) achieved TI; these rates were 45.7%, 42.9% and 44.4% at 6, 9, and 12 months, respectively. Furthermore, the rate of TI was 49.3% among JAK inhibitor–exposed patients vs 31.6% in JAK inhibitor–naive patients. Among patients who remained TD, the median number of red blood cell (RBC) units per month decreased from 4 to 2.25.
Of those evaluable for spleen response (n = 45), 62.2% of patients experienced an improvement in spleen size with a median reduction of 5 cm. However, only 24.4% of patients met the European LeukemiaNet (ELN) International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria for spleen response, and these patients had a median reduction of 10 cm). Notably, 26.7% of patients (n = 12) evaluable for spleen response maintained stable splenomegaly without a significant decrease; 3 patients showed refractoriness, and 2 experienced an increase in spleen size.
Flonoltinib Maleate Provides Durable Spleen Reduction and Symptom Improvement in Myelofibrosis
Treatment with the triple-target JAK2/FLT3/CDK6 inhibitor flonoltinib maleate produced significant, durable reductions in splenomegaly and improved symptom response for patients with myelofibrosis, according to data from a first-in-human phase 1/2a study (NCT05153343) presented during the 2024 ASH Annual Meeting.
As of the data cutoff of September 5, 2024, 77.3% of evaluable patients (n = 22) in the overall study population (n = 30) achieved at least a 35% reduction in spleen volume (SVR35) from baseline at 24 weeks. Two patients achieved SVR35 during cycles 22 and 24, respectively. The best spleen response rate in the overall population was 86.7%, and 76.7% of patients experienced at least a 50% reduction in total symptom burden (TSS50). Bone marrow fibrosis improvement was also observed in 26.1% of patients.
