Novel BET Inhibitor for Advanced Myelofibrosis

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Researchers may have uncovered a new type of targeted therapy for patients with advanced myelofibrosis, according to new findings presented by Watts et al at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 750).


Historically, there have been few standard treatments available for patients with advanced myelofibrosis, a bone marrow disorder characterized by excessive scar tissue that disrupts the normal production of blood cells.

The targeted and orally bioavailable epigenetic inhibitor of Bromodomain and extra-terminal (BET) proteins is designed to regulate the expression of critical oncoproteins involved in the disease process underlying hematologic malignancies such as myelofibrosis.

“It’s exciting to be part of this multicenter study because we’re seeing some encouraging results for a new type of targeted therapy for advanced myelofibrosis and other [hematologic] malignancies,” emphasized lead study author Justin M. Watts, MD, a hematologist at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine.

Study Methods and Results

In the new phase I dose-escalation/expansion study, the researchers analyzed the efficacy of the BET inhibitor INCB057643 as monotherapy in patients with relapsed or refractory advanced myelofibrosis or other advanced hematologic malignancies or in combination with the Janus kinase (JAK) inhibitor ruxolitinib in patients who did not respond to first-line therapy with ruxolitinib.

The researchers discovered that the investigational agent was found to be safe, well tolerated, and effective at treating symptoms such as fatigue, bone pain, night sweats, and an enlarged spleen. Surprisingly, INCB057643 also proved capable of treating anemia in some patients for whom previous treatment with JAK inhibitor monotherapy or combination therapy was unsuccessful.

“That’s really exciting because anemia is often a major problem with these patients, and it usually gets worse, not better, with additional treatment. We’ve had patients who were needing biweekly transfusions become transfusion-independent while on this targeted therapy,” Dr. Watts noted.

Additionally, the researchers were able to dose the novel therapy at a level that did not produce the side effects seen with some other BET inhibitors while still producing the desired outcomes.


“It really has an unexpectantly good therapeutic window, especially when given in combination with the standard-of-care drug ruxolitinib. We’re seeing good clinical results without the side effects,” Dr. Watts underscored.

The researchers plan to complete the phase I study in multiple, expanded cohorts for myelofibrosis and other hematologic malignancies. They then hope to move to a randomized, phase III trial examining the efficacy of INCB057643 in combination with ruxolitinib vs placebo to determine its ability to improve survival rates among these patients.

“Epigenetic-targeted therapies really work for many of the patients we treat in our clinics, and in general, have fewer side [effects] than chemotherapy. [T]hat’s both exciting and gratifying,” Dr. Watts concluded.

Disclosure: For full disclosures of the study authors, visit

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