James M. Rossetti, DO, hematologist, UPMC Hillman Cancer Center, discusses the utility of JAK inhibitors in myeloproliferative neoplasms (MPNs).

Long-term data from the phase III COMFORT-I and COMFORT-II trials and, more recently, the phase III RESPONSE trial have demonstrated the utility of ruxolitinib (Jakafi) in myelofibrosis and polycythemia vera, respectively.

However, ruxolitinib wasn’t widely adopted when it was first introduced due to the lack of long-term data versus hydroxyurea and busulfan, says Rossetti.

In August 2019, the FDA approved fedratinib (Inrebic) for the treatment of patients with myelofibrosis. Fedratinib is an important addition to the armamentarium as there are limitations to ruxolitinib’s utility, says Rossetti.

As with ruxolitinib, long-term data and institutional experience with fedratinib will help cement its utility in the field, concludes Rossetti.

Videos

James M. Rossetti, DO, discusses the utility of JAK inhibitors in myeloproliferative neoplasms.


Dr. Rossetti on the Utility of JAK Inhibitors in MPNs

James M. Rossetti, DO, hematologist, UPMC Hillman Cancer Center, discusses the FDA’s decision to grant momelotinib a fast track designation for use in patients with intermediate- or high-risk myelofibrosis who previously received a JAK inhibitor.

One of the concerns with agents such as momelotinib is dismissing them too early, says Rossetti. Sometimes, agents are dismissed due to the design of the trial, but other times the dismissal is due to selecting the wrong patient population, explains Rossetti.

This group of patients who received momelotinib in the phase III MOMENTUM trial is difficult to study because the they are heterogeneous, making analysis more challenging. Long-term follow-up becomes the key, according to Rossetti; however, the responsible use of these agents that get to market is going to make a difference in the long-run because it is very hard to prove long-term benefit in small clinical trials, Rossetti concludes.

James M. Rossetti, DO, discusses the FDA’s decision to grant momelotinib a fast track designation for use in patients with intermediate- or high-risk myelofibrosis who previously received a JAK inhibitor.

Dr. Rossetti on the Fast Track Designation of Momelotinib in Myelofibrosis

James M. Rossetti, DO, hematologist, UPMC Hillman Cancer Center, discusses symptom management for patients with myeloproliferative neoplasms (MPNs).

Symptom management largely relates to the disease that the person has, explains Rossetti. The patient needs to have their symptoms assessed to see which ones might be related to the disease. According to Rossetti, many patients with MPNs feel they do not receive an accurate diagnosis for several years with vague symptoms. Even low-risk disease can cause significant symptoms, including cytokine release syndrome and others.

Some agents, such as ruxolitinib (Jakafi), help with symptom management in patients with myelofibrosis and polycythemia vera. Aspirin can also manage many symptoms, according to Rossetti. Ultimately, looking at other antiplatelet therapies and looking at new agents might help patients with MPNs with their symptoms, concludes Rossetti.

James M. Rossetti, DO, discusses symptom management for patients with myeloproliferative neoplasms.

Dr. Rossetti on Symptom Management for MPNs

Assessing patients to understand their disease-related symptoms is an important step at diagnosis, explains Rossetti. Often, patients with MPNs present with vague symptoms for many years prior to diagnosis.

Significant disease-related symptoms resulting from cytokine release can occur, even in patients with low-risk disease, says Rossetti. 

In terms of symptom management, available agents like ruxolitinib (Jakafi) have helped alleviate symptoms in some patients with myelofibrosis and polycythemia vera, says Rossetti. Aspirin and other antiplatelet therapies are additional agents worth considering for patients, concludes Rossetti.

Dr. Rossetti on Symptom Management for Patients With MPNs

James M. Rossetti, DO, hematologist, UPMC Hillman Cancer Center, discusses risk stratification in myeloproliferative neoplasms (MPNs).

Risk stratification is crucial in assessing what patients are experiencing, says Rossetti. In those with polycythemia vera, for example, it’s important that past events such as cardiovascular risk factors are evaluated. It is easy to ask whether patients have had a pulmonary embolism and overlook other risk factors that they might have increased their risk for thrombosis. In order to get a complete picture, molecular profiling is done, as it relates to risk for transformation and as it relates to risk for thrombosis. All of this information is considered in the context of blood counts and cytogenetic modeling, explains Rossetti.

In myelofibrosis, the Dynamic International Prognostic Scoring System plus score is used frequently. With all of these new evolving models, providers are learning more about how to integrate information in a more succinct way. Such efforts will continue to evolve to ensure that patients are being stratified appropriately, concludes Rossetti.

James M. Rossetti, DO

Articles

Dr. Rossetti on the Utility of JAK Inhibitors in MPNs

Dr. Rossetti on the Fast Track Designation of Momelotinib in Myelofibrosis

Dr. Rossetti on Symptom Management for MPNs

Dr. Rossetti on Symptom Management for Patients With MPNs

Dr. Rossetti on Risk Stratification in Myeloproliferative Neoplasms