Post Hoc Data Show Anemia Benefits, Reduced Transfusion Burden With Momelotinib in Myelofibrosis

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A post hoc analysis of a single-arm, phase 2 study (NCT02515630) and the phase 3 SIMPLIFY-1 (NCT01969838), SIMPLIFY-2 (NCT02101268), and MOMENTUM (NCT04173494) studies showed that momelotinib (Ojjaara) was associated with anemia-related benefits in most patients and a reduction in transfusion burden vs comparator treatments in patients with JAK inhibitor–naive and –experienced myelofibrosis.1

Findings published in Clinical Lymphoma, Myeloma & Leukemia showed that more than 77% of patients treated with momelotinib across the 4 trials experienced a numerical reduction in red blood cell (RBC) transfusion requirements during treatment compared with baseline.

“This [post hoc analysis] demonstrates that across all 3 phase 3 trials of momelotinib in myelofibrosis to date, at least 75% of patients treated with momelotinib either maintained or experienced improved transfusion intensities vs baseline,” lead study author Claire Harrison, MD, FRCP, FRCPath, a professor of myeloproliferative neoplasm and clinical director of Guy’s and St Thomas’ NHS Foundation Trust in London, United Kingdom, and colleagues wrote in the publication. “These results provide evidence that underscores the consistent anemia benefits provided by momelotinib for the majority of patients.”

In September 2023, the FDA approved momelotinib for the treatment of adult patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis, and anemia.2 This regulatory decision was supported by data from MOMENTUM and a subgroup of patients with anemia treated during SIMPLIFY-1.

Post Hoc Analysis Rationale and Design

Although data regarding transfusion independence response rates from MOMENTUM, SIMPLIFY-1, and SIMPLIFY-2 have underscored the anemia benefit associated with momelotinib in myelofibrosis, Harrison and colleagues explained that this post hoc analysis aimed to better characterize the relative anemia-related benefits associated with the agent.1

As a proof of concept, investigators first assessed time-dependent transfusion burden in patients treated in the phase 2 study before conducting further analyses using findings from the 3 phase 3 studies. They collected data on RBC units transfused and hemoglobin (Hb) levels associated with transfusions during the 24-week study period and at baseline before the initiation of momelotinib. Baseline was defined as 56 days prior to enrollment in the phase 2 study and 84 days before enrollment in each of the phase 3 trials. Patients from the phase 3 studies who received less than 14 days of treatment were excluded from the analysis.

Time-dependent transfusion burden—defined as the number of RBC units administered in a 28-day period—was tracked for each patient, along with mean transfusion intensities at baseline and during treatment. Patients were also grouped based on RBC unit intensity at baseline and during treatment; the bins included those who received. 0 units, more than 0 to less than 1 units, more than 1 to less than 2 units, more than 2 to less than 3 units, more than 3 to less than 4 units, or more than 4 units per 28 days.

Phase 2 Results

The open-label, translational biology, phase 2 study enrolled patients with intermediate- or high-risk myelofibrosis who were transfusion dependent, defined as receiving at least 4 RBC units in the 8 weeks prior to the first dose of study treatment. All patients received momelotinib at 200 mg once per day for up to 24 weeks.

Transfusion independence response by week 24, defined as no RBC transfusions for any period of at least 12 weeks during the study, served as the primary end point.

The post hoc analysis of the phase 2 study showed that patients with a known transfusion status (n = 40) were all transfusion dependent at baseline, and in the overall group (n = 41), 88% of patients were naive to JAK inhibitors. Patients in this group had a mean Hb level of 83 g/L, and 71% of patients had a Hb level of at least 80 g/L. At baseline, patients had a mean RBC transfusion requirement of 3.2 units (range, 1.5-6.0) per 28 days, and this decreased to 1.7 units (range, 0-6) during treatment (mean change, 1.5; standard deviation [SD], 1.3).

Additionally, 85% of patients experienced a reduction in RBC transfusion intensity during treatment vs baseline. Among patients who became transfusion free (n = 9), 78% were transfusion independence responders.

SIMPLIFY-1

The phase 3, double-blind, double-dummy study enrolled patients with JAK inhibitor–naive, intermediate-1–, intermediate-2–, or high-risk myelofibrosis with palpable splenomegaly at least 5 cm below the left costal margin who were randomly assigned in a 1:1 fashion to receive momelotinib plus placebo twice per day or ruxolitinib (Jakafi) plus placebo.3 After the 24-week double-blind treatment phase, all patients were eligible to receive open-label momelotinib for up to an additional 216 weeks.

Splenic response rate served as the trial’s primary end point, and transfusion independence response rate at week 24 was a key secondary end point.1

At baseline, 25% of patients in the momelotinib arm (n = 215) and 24% of those in the ruxolitinib arm (n = 217) were transfusion dependent at baseline. The rates of patients with a Hb level of at least 80 g/L at baseline were 87% and 90%, respectively.

The mean transfusion intensities at baseline were in 0.5 units (range, 0-6.7) per 28 days in the momelotinib arm and 0.5 units (range, 0-5.3) per 28 days in the ruxolitinib arm. During treatment, the mean transfusion intensity dropped to 0.4 units (range, 0-7.8) per 28 days in the momelotinib arm and increased to 0.9 units (range, 0-7.0) per 28 days in the ruxolitinib arm. The mean RBC transfusion burden changes were –0.10 units (SD, 0.7) per 28 days in the momelotinib arm vs 0.39 units (SD, 1.0) per 28 days in the ruxolitinib arm.

In the momelotinib arm, 95% of patients who were transfusion free at baseline (n = 150) remained transfusion free during the treatment period compared with 57% of patients in the ruxolitinib arm (n = 163). Twenty-nine percent of patients in the momelotinib arm who had some transfusion burden at baseline (n = 63) became transfusion free vs 13% of these patients in the ruxolitinib arm (n = 53).

The rates of patients in the momelotinib arm (n = 213) who had improved and stable RBC transfusion intensities were 19% and 68%, respectively. These respective rates in the ruxolitinib arm (n = 216) were 11% and 44%.

MOMENTUM

This phase 3 trial was a double-blind, placebo-controlled study that enrolled patients with symptomatic, JAK inhibitor–experienced myelofibrosis who were randomly assigned 2:1 to receive momelotinib plus placebo or danazol plus placebo. Total symptom score response rate was this trial’s primary end point, and transfusion independence response rate was a key secondary end point.

The rates of transfusion independence at baseline were 48% for the momelotinib arm (n = 130) vs 52% for the danazol arm (n = 65). The respective rates of patients with Hb levels of at least 80 g/L at baseline were 52% and 51%.

The mean transfusion intensities at baseline were 2.0 units (range, 0-10.3) per 28 days in the momelotinib arm compared with 2.2 units (range, 0-9.7) per 28 days for danazol. The mean transfusion intensities during the treatment were reduced to 1.1 units (range, 0-6.3) per 28 days for momelotinib vs 1.9 units (range, 0-11.2) per 28 days in the danazol arm. The reductions in mean RBC transfusion burdens per 28 days were −0.86 units (SD, 1.7) and −0.28 units (SD, 1.6), respectively.

After 20% of patients in the momelotinib arm and 17% of those in the danazol arm were transfusion free at baseline, 35% and 17% of patients, respectively, were transfusion free during treatment. Transfusion-free status at baseline was maintained by 92% of patients in the momelotinib arm (n = 26) vs 64% of patients in the danazol arm (n = 11). In patients in the momelotinib group (n = 104) and danazol group (n = 54) who had some transfusion burden at baseline, 21% and 7%, respectively, became transfusion free for the duration of the treatment period.

The rates of improved and stable RBC transfusion intensities were 65% and 19%, respectively, for the momelotinib arm. These respective rates were 52% and 11% in the danazol arm.

SIMPLIFY-2

The open-label SIMPLIFY-2 trial included patients with JAK inhibitor–experienced myelofibrosis who were randomly assigned 2:1 to receive momelotinib or best available therapy (BAT), including 88.5% who were given ruxolitinib. Splenic response rate was the primary end point, with transfusion independence response rate serving as a key secondary end point.

At baseline, the rates of transfusion dependence were 56% in the momelotinib arm (n = 104) and 52% in the BAT arm (n = 52). The respective rates of patients with a baseline Hb level of 80 g/L or higher were 74% and 89%.

The mean transfusion intensity at baseline was 1.4 units (range, 0-7.0) per 28 days in the momelotinib arm vs 1.3 units (range, 0-5.0) in the BAT arm. During treatment, these respective intensities were 1.1 units (range 0-6.0) per 28 days and 1.3 units (range, 0-6.7) per 28 days. The changes in mean RBC transfusion burden per 28 days were −0.36 units (SD, 1.4) and 0 units (SD, 1.3), respectively.

Thirty-six percent of patients in the momelotinib arm were transfusion free at baseline compared with 37% of patients in the BAT arm. During the treatment period, the rates of patients who were transfusion free for the entire treatment period were 44% and 27%, respectively. This status was maintained from baseline in 76% of patients in the momelotinib arm (n = 37) vs 63% of patients in the BAT arm (n = 19). In patients with some transfusion burden at baseline, 26% and 6% in the momelotinib (n = 66) and BAT (n = 33) arms became transfusion free for the entire treatment period.

Improved or stable RBC transfusion intensities were observed in 49% and 28% of patients, respectively, in the momelotinib arm. These respective rates were 39% and 23% in the BAT arm.

References

1. Harrison CN, Mesa R, Talpaz M, et al. Longitudinal assessment of transfusion intensity in patients with JAK inhibitor-naive or -experienced myelofibrosis treated with momelotinib. Clin Lymphoma Myeloma Leuk. 2025;25(3):199-211. doi:10.1016/j.clml.2024.10.001
2. Ojaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia. News release. GSK. September 15, 2023. Accessed May 22, 2025. https://www.gsk.com/en-gb/media/press-releases/ojjaara-momelotinib-approved-in-the-us-as-the-first-and-only-treatment-indicated-for-myelofibrosis-patients-with-anaemia
3. Momelotinib versus ruxolitinib in subjects with myelofibrosis (Simplify 1). ClinicalTrials.gov. Updated May. 12, 2023. Accessed May 22, 2205. https://clinicaltrials.gov/study/NCT01969838