Introduction: Anemia is a prevalent and progressive manifestation of myelofibrosis (MF) with substantial impacts on patient quality of life and survival. Hemoglobin (Hb) levels of <10 g/dL are included as a negative prognostic factor in all major MF risk assessment tools, while achieving Hb improvements may be associated with improved overall survival (OS). A recent analysis of the phase 3 SIMPLIFY-1 and MOMENTUM trials of the JAK1/JAK2/ACVR1 inhibitor momelotinib, which is approved for the treatment of patients with MF and anemia, found that achievement of Hb ≥10 g/dL is associated with longer OS with momelotinib (Palandri F, et al. EHA 2025. Poster PF828). The current analysis aims to characterize the relationship between momelotinib exposure and Hb improvement, as well as the time needed to achieve an improvement of ≥1 g/dL, in the MOMENTUM patient population, in which all patients had Hb <10 g/dL at baseline.

Methods:MOMENTUM (NCT04173494) was a randomized phase 3 trial of momelotinib vs danazol in symptomatic (Total Symptom Score ≥10) and anemic (Hb <10 g/dL), JAK inhibitor–experienced patients with MF. All patients initiated momelotinib at the now-approved dose of 200 mg once daily. This post hoc analysis was conducted in the pharmacokinetic (PK) analysis set who received ≥1 dose of momelotinib and had ≥1 nonmissing postdose concentration value (n=111). Analyses included evaluation of mean percent change from baseline in Hb levels every 4 weeks through week 24 and Kaplan-Meier curves to assess time to Hb improvement of ≥1 g/dL from baseline relevant to momelotinib exposure. In both analyses, data were summarized across exposure quartiles (Q1-Q4) of momelotinib based on the area under the curve at steady state (AUCss), with each quartile containing approximately 25% of patients across the range of AUCss observed from lowest (Q1) to highest (Q4).

Results: Among the 111 patients in MOMENTUM who were included in the PK analysis set, 96 (86%) were evaluable; thus, each momelotinib exposure quartile consisted of 24 patients. Mean Hb levels increased from baseline in all quartiles by week 4; mean (95% CI) percent changes from baseline at week 4 were 13.12% (2.93%-23.31%), 7.97% (2.08%-13.86%), 11.20% (5.28%-17.13%), and 15.76% (9.25%-22.27%) in Q1, Q2, Q3, and Q4, respectively. Mean Hb levels remained higher than baseline in all quartiles through week 24, with respective mean (95% CI) percent changes from baseline at week 24 of 8.07% (−2.38% to 18.51%), 12.23% (0.01%-24.45%), 16.81% (8.78%-24.85%), and 11.22% (2.32%-20.13%); however, the Q1 95% CI crossed 0, suggesting that patients in this lowest exposure quartile were less likely to maintain Hb improvement.

In the time-to-event analysis, 66 of 96 patients overall (69%) achieved an Hb improvement of ≥1 g/dL. Approximately 50% of patients in all quartiles achieved this threshold by week 2 (first postbaseline assessment); however, the number of additional patients achieving this threshold at each subsequent assessment increased with increasing momelotinib exposure. All patients in Q4 (the highest exposure quartile) achieved an Hb improvement of ≥1 g/dL by week 8; in Q3 (which contains the approximate midrange of the AUCss for the 200-mg daily dose), the time for all patients to achieve an Hb improvement of ≥1 g/dL was 12 weeks, and in Q1/Q2 it was 24 weeks.

Conclusions: In JAK inhibitor–experienced patients with baseline Hb <10 g/dL, higher momelotinib exposure was associated with greater anemia-related benefits, including maintenance of increased Hb from baseline and faster time to Hb improvement of ≥1 g/dL. The benefits were more pronounced in the higher quartiles of AUCss (Q3-Q4), highlighting the fact that initiation and maintenance of the full 200-mg daily dose of momelotinib in line with prescribing information is necessary to ensure optimal outcomes in this patient population.

This content is only available as a PDF.
2025
Sign in via your Institution