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BM fibrosis changes with JAK inhibition in MF

Jan 26, 2023
Learning objective: After reading this article, learners will be able to cite a new clinical development in myelofibrosis.

Bone marrow fibrosis (BMF) is a primary feature of myelofibrosis (MF) and is often associated with poor prognosis.1 While there are limited data on the association between BMF changes and clinical efficacy of MF treatments, improvement in fibrosis has shown evidence of disease modification.1

During the 64th American Society of Hematology (ASH) Annual Meeting and Exposition, Oh1 provided a presentation on the effects of ruxolitinib and momelotinib on BMF, as well as an analysis of the correlation between BMF changes and outcomes in Janus kinase (JAK) inhibitor-naïve patients with MF from the phase III SIMIPLIFY-1 study (NCT01969838). The SIMPLIFY-1 study design has previously been reported on the MPN Hub, and we are pleased to summarize the key findings presented by Oh1 below.


At baseline, 58% of patients in both the momelotinib and ruxolitinib treatment groups had Grade 3 BMF. Moreover, when paired samples were analyzed, both momelotinib and ruxolitinib had similar effects on Grade ≥1 improvement in BMF (Figure 1).

Figure 1. Baseline grade improvements in momelotinib- and ruxolitinib-treated patients* 

BMF, bone marrow fibrosis.
*Data from Oh.1

There was no association between BMF changes and Week 24 symptom responses or spleen responses for either momelotinib- or ruxolitinib-treated patients (Figure 2).

Figure 2. BMF changes and A) Week 24 symptom responses and B) spleen responses in momelotinib- and ruxolitinib-treated patients* 

BMF, bone marrow fibrosis.
*Adapted from Oh.1

A total of 78% of patients treated with momelotinib had a Week 24 transfusion independence (TI) response (p = 0.3503), which was defined as the absence of red blood cell transfusions and no hemoglobin levels <8 g/dL in the 12 weeks before Week 12. In comparison, 53% of patients treated with ruxolitinib had a Week 24 TI response (p = 0.0963). Similar TI responses were recorded in both treatment groups with worsening BMF. In contrast, hemoglobin concentrations increased during momelotinib treatment, but decreased during ruxolitinib treatment despite worsening of BMF (Figure 3). Changes in BMF were also not associated with overall survival.

Figure 3. Average hemoglobin concentrations at baseline and Week 24 for patients treated with momelotinib and ruxolitinib* 

Hgb, hemoglobin.
*Adapted from Oh.1


In conclusion, BMF changes at Week 24 did not correlate with symptom or spleen response, anemia improvement, or overall survival in patients treated with momelotinib or ruxolitinib. However, 20% of patients who were JAK inhibitor naïve had a ≥1 grade BMF improvement within 24 weeks when treated with either drug. Collectively, these results highlight the need for better understanding of BMF changes by Week 24 of treatment and whether bone marrow assessment at Week 24 is of clinical benefit.

Expert Opinion

“I think there are many limitations on bone marrow fibrosis as an endpoint in studies, mainly with the validity of the scoring together with its limited levels,” said Dr Mesa, Executive Director of Atrium Health Wake Forest Baptist Comprehensive Cancer Center and co-author of the SIMPLIFY-1 study. “Medical therapies up to this point have not made a dramatic difference at a high level to fibrosis, and so there is not much surprise that there is no strong correlation between other markers of response and fibrosis.”

  1. Oh S. Bone marrow fibrosis changes do not correlate with efficacy outcomes in myelofibrosis: Analysis of more than 300 JAK inhibitor-naïve patients treated with momelotinib or ruxolitinib. Oral abstract #337. 64th American Society of Hematology Annual Meeting and Exposition; Dec 10, 2022; New Orleans, US.