Ruben A. Mesa, MD, director of the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, discusses the potential role of momelotinib in alleviating myelofibrosis-associated anemia.

Anemia is a common symptom of myelofibrosis, says Mesa. JAK inhibitors, such as ruxolitinib (Jakafi) and fedratinib (Inrebic), may exacerbate anemia. 

Despite this, the JAK inhibitor momelotinib is also an ACVR1 inhibitor, which could play a role in decreasing hepcidin, Mesa explains. Furthermore, hepcidin is thought to contribute to anemia and suppress hematopoiesis when found in an inflammatory environment. By decreasing hepcidin, momelotinib may improve erythropoiesis and anemia.

FDA granted a fast track designation to momelotinib

 for use as a treatment of patients with intermediate- or high-risk myelofibrosis who had previously received a JAK inhibitor 

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Ruben A. Mesa, MD, discusses the potential role of momelotinib in alleviating myelofibrosis-associated anemia.  



Dr. Mesa on the Potential Role of Momelotinib for Myelofibrosis-Associated Anemia 

Ruben A. Mesa, MD, director of the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, discusses management strategies for patients with myeloproliferative neoplasms (MPNs).

Patients with MPNs can be separated into 2 different groups: There are those who have early disease with essential thrombocythemia and polycythemia vera (PV), where the management is focused on trying to decrease the risk of thrombosis and bleeding. Management strategies for these patients include theuse of aspirin, selective use of phlebotomy for patients with PV, cytoreduction with an interplay of hydroxyurea, pegylated interferon-a2 (PEG-IFNa2; Pegasys), and JAK inhibitors, such as ruxolitinib (Jakafi).

Patients with myelofibrosis, however, have more life-threatening conditions and tend to have a higher burden of disease with splenomegaly symptoms and cytopenias. They also have a much higher risk of disease-related mortality. There is a balance between the timing of stem cell transplantation and medical therapy. The field now has 2 approved therapies, ruxolitinib and fedratinib (Inrebic), with several other JAK inhibitors following close behind in the pipeline, including momelotinib (formerly GS-0387, CYT-387) and pacritinib. Other exciting new therapies and combinations are forthcoming, as well, concludes Mesa.

Ruben A. Mesa, MD, discusses management strategies for patients with myeloproliferative neoplasms.

Dr. Mesa on Management Strategies for MPNs

Ruben A. Mesa, MD, director of the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, discusses remaining challenges faced in the treatment of patients with myeloproliferative neoplasms (MPNs).

The issue of progression in MPNs is quite challenging, says Mesa. Although more active primary therapies have emerged in recent years, the field has not achieved a state of remission or cure with the current therapies that are available, according to Mesa. More work needs to be done to improve efficacy, Mesa adds.

Better disease control is being achieved but these diseases are still not being cured, nor are all patients achieving a minimal residual disease state, says Mesa. There are some biological lessons to learn in terms of understanding drivers of progression and how to further avoid disease progression in MPNs. It is essential to understand the mechanisms of action and evaluate combination therapies moving forward, concludes Mesa.

Ruben A. Mesa, MD, discusses remaining challenges faced in the treatment of patients with myeloproliferative neoplasms.
 

Dr. Mesa on Remaining Challenges Faced in MPN Treatment

Ruben A. Mesa, MD, director of the Mays Cancer Center at the University of Texas Health San Antonio MD Anderson Cancer Center, discusses the emergence of JAK inhibitors in myelofibrosis. 

Initially, JAK inhibitors were tested in patients with poor prognosis, explains Mesa.

Now, 2 JAK inhibitors, ruxolitinib (Jakafi) and fedratinib (Inrebic)​, are approv​ed for the treatment of patients with myelofibrosis. Notably, ruxolitinib is a JAK1/2 inhibitor, whereas fedratinib specifically ​inhibits JAK2. 

JAK inhibitors are increasingly being used in early-stage disease, wherein they are showing equal value in mitigating disease-related symptoms, Mesa concludes. 

Ruben A. Mesa, MD, discusses the emergence of JAK inhibitors in myelofibrosis. 








Dr. Mesa on the Emergence of JAK Inhibitors in Myelofibrosis

Ruben A. Mesa, MD, director of the Mays Cancer Center at University of Texas Health San Antonio MD Anderson Cancer Center, discusses current data with ruxolitinib (Jakafi) and fedratinib (Inrebic) in myelofibrosis.

Two agents are commercially available for patients with myelofibrosis, says Mesa. First, there is ruxolitinib, which is now included in the National Comprehensive Cancer Network (NCCN) guidelines. Real-world data and expanded access data on the safety of the agent in earlier-stage myelofibrosis are now available, adds Mesa. It certainly is a recommended consideration in those with symptomatic lower-risk myelofibrosis, as well as intermediate-1 myelofibrosis with splenomegaly and/or symptoms.

Fedratinib has also emerged in this space, says Mesa. However, less data on this agent in this patient population are available because when fedratinib was approved, there was a period of time where it had been on a clinical hold. This means expanded access trials were not performed with fedratinib, which may have included patients who had lower-risk symptomatic or intermediate-1 risk disease. The current NCCN guidelines do not recommend that group of patients for fedratinib; however, over time, more experience will be gained and it is possible that the agent will be found to benefit those patients, as well, concludes Mesa.

Ruben A. Mesa, MD, discusses current data with ruxolitinib and fedratinib in myelofibrosis.

Dr. Mesa on Current Data With Ruxolitinib and Fedratinib in Myelofibrosis

Ruben A. Mesa, MD, director of the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, discusses accrual considerations in myeloproliferative neoplasms (MPN) clinical trials. 

The Mays Cancer Center is based in San Antonio, ​Texas, where about 69% of the population is Hispanic or Latino, says Mesa​. The patient populations that are included in clinical trials should be representative of the surrounding community.

To date, clinical trials at UT San Antonio MD Anderson Cancer Center include a high percentage of Hispanic patients, ​Mesa explains. Additionally, other minority groups, such as African Americans represent a high percentage of the overall population in these studies. 

Notably, ​considerations are taken to ​develop a racially​-inclusive ​patient population, starting with accrual. Barriers are continually being overcome with time and teamwork, Mesa concludes. 

Ruben A. Mesa, MD, discusses accrual considerations in myeloproliferative neoplasms  clinical trials. 

Dr. Mesa on Accrual Considerations in MPN Clinical Trials  

Ruben A. Mesa, MD, director of the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, discusses the importance of developing racially inclusive clinical trials in myeloproliferative neoplasms (MPNs).

According to Mesa, teamwork plays a key role in diversifying clinical trials.

The combined efforts of FDA stakeholders, pharmaceutical representatives, medical community members, academic centers, third-party payers, and patient advocacy groups are needed to continue the national conversation regarding the importance of diversity in clinical trials, Mesa explains.

Although significant work is needed, developing racially inclusive clinical trials could result in more broadly applicable data, concludes Mesa.

Ruben A. Mesa, MD, discusses the importance of developing racially inclusive clinical trials in myeloproliferative neoplasms.  



Dr. Mesa on Developing Racially Inclusive Clinical Trials in MPNs 

Ruben A. Mesa, MD, director of the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, discusses racial disparities in clinical trials for patients with myeloproliferative neoplasms(MPNs), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML).

Clinical trials for patients with MPNs, MDS, and AML lack diversity, says Mesa. Notably, these challenges are similar to those faced in solid tumor studies. 

Some contributing factors ​to the lack of diverse patient accrual include lack of access to clinical trials and financial limitations. 

Moreover, if travel is required, patients must have the financial flexibility to do so​, along with the ability to request time off of work. ​Lack of awareness and ​limited health literacy ​could also be barriers to enrolling a diverse group of patients, Mesa concludes. 

Ruben A. Mesa, MD, discusses racial disparities in clinical trials for patients with myeloproliferative neoplasms, myelodysplastic syndrome, and acute myeloid leukemia.

Dr. Mesa on Racial Disparities in MPN, MDS, and AML Clinical Trials 

Ruben A. Mesa, MD, director of the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, discusses the potential utility of CAR T-​cell ​therapy in myeloproliferative neoplasms (MPNs).

In recent years, cellular therapy has evolved rapidly in lymphoid malignancies, especially in lymphoma and ​multiple myeloma, says Mesa.

Notably, at the Institutional Perspectives in Cancer webinar on Leukemia and Lymphoma, Paul ​J. Shaughnessy, MD, of Methodist Hospital, expanded on these data and provided insight on future directions of CAR T-cell therapy ​in hematologic malignancies.

The utility of cellular-based therapy, in both hematologic and non-hematologic malignancies, has sparked great interest ​across oncology. Encouraging data suggest CAR T-cell therapy may soon find a place in the MPNs space, ​concludes Mesa.

Ruben A. Mesa, MD, discusses the potential utility of CAR T-​cell ​therapy in myeloproliferative neoplasms.

Dr. Mesa on the Potential Utility of CAR T-Cell Therapy in MPNs 

Ruben A. Mesa, MD, director of the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, discusses the potential clinical benefit of rechallenging with JAK inhibitor therapy in patients with myeloproliferative neoplasms (MPNs).

Preclinical and anecdotal data ​suggest that holding ruxolitinib (Jakafi) may yield some clinical benefit for patients, says Mesa.

Particularly, this method may have utility for patients who are ineligible for clinical trials or do not have access to fedratinib (Inrebic)​, Mesa explains.

​Determining whether a patient has disease progression is critical when considering this strategy as rechallenging with ruxolitinib may not be beneficial in patients who have not progressed, concludes Mesa.

Ruben A. Mesa, MD, discusses the potential clinical benefit of rechallenging with JAK inhibitor therapy in patients with myeloproliferative neoplasms.

Ruben A. Mesa, MD

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