Increasing understanding of the mechanisms of myelofibrosis facilitates the introduction of new treatments and novel agents.

According to Gabby Hobbs, MD, research providing an increased understanding of the molecular mechanisms of myelofibrosis has helped facilitate the development of new treatments for this patient population, and novel agents are poised to emerge in this field.

In February 2022, FDA-approved pacritinib (Vonzo) For the treatment of patients with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with platelet counts less than 50 × 109/l.1 moreover, Regulatory agency approves momelotinib (Ojjara) In September 2023 for the treatment of patients with primary myelofibrosis or intermediate- or high-risk myelofibrosis, including secondary myelofibrosis and anemia.2 Both agents inhibit ACVR1, and their approvals are examples of how increasing understanding of the biology of myelofibrosis is informing drug development.

“We have a better understanding of many of the mechanisms involved in the development and pathophysiology of myelofibrosis,” Hobbs said in an interview. onclive Following the State of the Science Summit™ (SOSS) on Hematology, which he chaired.

In the interview, Hobbs discussed how further research into the biology of myelofibrosis has led to the development of novel treatments for this patient population, expanded on ongoing and upcoming investigations of various agents, and improved diagnosis, prognosis. and has highlighted the role of biomarkers in diagnosis. Treatment response assessment for these patients. Hobbs is a hematology-oncology physician, clinical director of the leukemia service, and assistant in medicine at Massachusetts General Hospital in Boston.

onclive: Your presentations at SOSS focused on the emerging treatment landscape of myelofibrosis and current standards of care. What were the key points you tried to highlight during these discussions?

Hobbs: There have been a lot of changes in the treatments available (for patients with myelofibrosis) over the years. The first presentation focused on providing a brief overview of the current standard of care and new treatments available for myelofibrosis (treatment of patients).

The second discussion (focused) on an area where there are still a lot of unmet needs, which is anemia, (and I wanted to) give the audience an idea or perspective on how to manage anemia for these patients, especially Since (after) the approval of momelotinib.

What is the current understanding of the molecular mechanisms of myelofibrosis? How has this influenced the development of personalized treatment strategies for this patient population?

(Increased understanding of the mechanisms of myelofibrosis) has helped lead to the approval of some new drugs, including pacritinib and momelotinib. We (previously) mostly focused on the JAK/STAT signaling pathway; We now appreciate that there are other signaling pathways that may be involved in the pathophysiology of this disease.

For example, momelotinib and pacritinib also inhibit the ACVR1 pathway, thereby improving anemia. This is a very clear way that we have improved treatments based on a better understanding of the biology of[myelofibrosis].

In addition to momelotinib and pacritinib, are there any other agents currently under investigation in myelofibrosis that are of interest?

There are several different agents that are currently being studied. The one that is probably closest to being available to patients is lespatercept-AMT (Reblozil), as it is already approved for patients with myelodysplastic syndrome, and it will particularly help patients suffering from anemia. With respect to other novel treatments, there are several agents that are currently under development, including drugs such as the telomerase inhibitor imetelstat, the Bcl-2/Bcl-xL inhibitor navitoclax, the BET inhibitor pelabresib (CPI-0610), the MDM2 inhibitor nevetamedlin . (formerly KRT-232), and the XPO1 inhibitor selinexor (Xpovio).

There are several agents now under development that may change the field of myelofibrosis from solely single-agent JAK inhibitors to combination therapies that can hopefully help our patients live with less symptoms and live longer. .

What role do biomarkers play in the diagnosis, prognosis, and treatment response assessment of patients with myelofibrosis?

When you look at what we call biomarkers in myelofibrosis, we rely significantly on genetic mutations and different types of risk scores to predict the prognosis for our patients. We know that with patients JAK2 The consequences of mutations are different from those CALR Mutation. More specifically, we know that additional mutations are occurring outside J A,state Mutations also contribute to a negative prognosis, and they include mutations such as ASXL1, human Development Index, srsf2And EZH1, Those genetic mutations help us understand the prognosis with these patients when taken in combination with other clinical variables included in the (risk) score.


  1. CTI BioPharma has announced FDA accelerated approval of VONJO™ (pacritinib) for the treatment of adult patients with myelofibrosis and thrombocytopenia. CTI BioPharma Corp. News Release. February 28, 2022. Accessed November 8, 2023.
  2. Ozara (momelotinib) has been approved in the US as the first and only treatment indicated for myelofibrosis patients suffering from anemia. News release. GlaxoSmithKline. September 15, 2023. Accessed November 8, 2023. -treatment-indicated

(TagstoTranslate)Gabby Hobbs(T)MD(T)Massachusetts General Hospital(T)Myelofibrosis

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