Andrew T. Kuykendall, MD, assistant member, Department of Malignant Hematology, Moffitt Cancer Center, discusses the potential for momelotinib in the treatment of patients with myelofibrosis.

Momelotinib is a JAK inhibitor that is currently under investigation in this patient population, and that has been associated with improvements in cytopenias, such as anemia, in the phase 3 Simplify 1 (NCT01969838) and Simplify 2 (NCT02101268) trials, according to Kuykendall. Additionally, the agent is being examined in the randomized phase 3 MOMENTUM trial (NCT04173494), where it is being compared with danazol, Kuykendall explains. 

The drug may have the potential to transform the treatment paradigm for patients who experience cytopenias and splenomegaly, as well as for those who need help managing anemia, spleen size, and other symptoms, Kuykendall adds. As such, the results of the trial are highly anticipated to determine whether momelotinib will be an option for these patients, Kuykendall concludes.

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Andrew T. Kuykendall, MD, discusses the potential for momelotinib in the treatment of patients with myelofibrosis.

Dr. Kuykendall on the Potential for Momelotinib in Myelofibrosis 

Andrew T. Kuykendall, MD, assistant member, Department of Malignant Hematology, Moffitt Cancer Center, discusses the addition of fedratinib (Inrebic) to the treatment paradigm in myelofibrosis.

Fedratinib is a relatively old drug that went through extensive clinical trials and was tested in many patients several years ago. After going through phase III clinical trials in ruxolitinib (Jakafi) patients with myelofibrosis, fedratinib was put on hold.

Despite its setbacks, fedratinib experienced a resurgence where the safety signals were reexamined, and researchers took a closer look at its efficacy. Now, fedratinib is approved to treat patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis, giving patients the option of a second JAK inhibitor.

Andrew T. Kuykendall, MD, discusses the additionof fedratinib to the treatment paradigm in myelofibrosis.

Dr. Kuykendall on the Approval of Fedratinib in Myelofibrosis

Andrew T. Kuykendall, MD, assistant member, Department of Malignant Hematology, Moffitt Cancer Center, discusses the use of ruxolitinib (Jakafi) versus fedratinib (Inrebic) in patients with myelofibrosis. 

Ruxolitinib is currently used in patients with intermediate- and high-risk disease as it has shown benefit in reducing disease-related symptoms and enlarged spleens. Although ruxolitinib has been shown to improve quality of life for patients, there is some debate regarding when to sequence the JAK1/JAK2 inhibitor. 

In August 2019, fedratinib was approved in the same indication as ruxolitinib, Kuykendall says. Head-to-head comparison of the agents may provide insight into which patient populations will benefit more from one drug versus the other. 

Notably, increased toxicity has been reported with fedratinib. These adverse events are mainly gastrointestinal in nature including nausea and diarrhea, Kuykendall concludes. 

Andrew T. Kuykendall, MD, discusses the use of ruxolitinib versus fedratinib in patients with myelofibrosis. 
 

Dr. Kuykendall on Choosing Ruxolitinib or Fedratinib in Myelofibrosis

Andrew T. Kuykendall, MD, assistant member, Moffitt Cancer Center, discusses the impact of ruxolitinib (Jakafi) in myeloproliferative neoplasms (MPNs).

Ruxolitinib has had a great impact across the field of MPNs, explains Kuykendall. It targets the JAK-STAT pathway, which is highly active in these neoplasms. It has shown the greatest impact in patients with myelofibrosis, says Kuykendall, as it has the only FDA indication in this disease. In very symptomatic patients, the agent can help resolve symptoms and get a patient back to feeling normal—–something that was not possible previously, explains Kuykendall. Physicians are still trying to understand the agent’s reach in the landscape in terms of its ability to improve transplant outcomes and why it enables survival benefits.

In polycythemia vera, it has added to the field—if not changed the landscape, says Kuykendall. It’s viewed among physicians as a great second-line therapy after hydroxyurea intolerance or failure. Patients are also very appreciative of the agent as it can also help lessen a patient’s symptomatic burden, explains Kuykendall.

Andrew T. Kuykendall, MD

Articles

Dr. Kuykendall on the Potential for Momelotinib in Myelofibrosis

Dr. Kuykendall on the Approval of Fedratinib in Myelofibrosis

Dr. Kuykendall on Choosing Ruxolitinib or Fedratinib in Myelofibrosis

Dr. Kuykendall on the Impact of Ruxolitinib in Myeloproliferative Neoplasms