Ruben Mesa, MD

Ruben Mesa, MD, director, Mays Cancer Center at The University of Texas Health San Antonio, MD Anderson Cancer Center San Antonio, TX, shares highlights from his presentation on the role of JAK inhibitors in myelofibrosis (MF) during the first annual Texas Virtual MPN Workshop and Meeting.

The key takeaway is to be incredibly hopeful for having such a robust set of therapies in development for the treatment of MF, many of which are active, credible treatments, Mesa says. Two years from now, we may have multiple approved agents that may have a variety of different pathways that might be individualized.

For patients with marked thrombocytopenia, you may give the patient pacritinib, or if they are transfusion-dependent, perhaps momelotinib upfront or ruxolitinib (Jakafi) and luspatercept (Reblozyl) or fedratinib (Inrebic) and luspatercept, Mesa adds. Patients with a certain high-risk mutation could start treatment with a JAK inhibitor and the BET inhibitor, or patients could be treated with ruxolitinib for 3 months and have a suboptimal response, so then they end up receiving venetoclax (Venclexta).

Mesa says treatment of MF will become more nuanced and much more individualized in time. He believes that the period of time a patient is on therapy before an evaluation will also change. In the future, we will likely have more concrete markers so that if patients do not achieve response in 3 or 6 months, physicians can try another therapeutic approach.

Videos

Ruben Mesa, MD, shares highlights from his presentation on the role of JAK inhibitors in myelofibrosis during the first annual Texas Virtual MPN Workshop and Meeting.

Treatment Approaches Become More Individualized as Field of Myelofibrosis Advances

Ruben Mesa, MD, director of Mays Cancer Center, home to UT Health San Antonio MD Anderson, discusses the role of JAK inhibitors, which are currently being investigated in patients with myelofibrosis. He also spoke to what the future of this treatment landscape may be.

Two JAK inhibitors that are in clinical trials at the moment are momelitinib and pacritinib, both of which Mesa believes may become available in the near future. He says that momelitinib may have differentiation around cytopenias and anemia compared to other JAK inhibitors in this setting; pacritinib may be safe for patients with thrombocytopenia. He hopes to see multiple JAK inhibitors available for this patient population in the future so that physicians can tailor their treatment more appropriately in the first- and second-line settings.

If momelitinib and pacritinib are approved, the other agents will have the potential to be used as combination therapy, according to Mesa. Agents such as navitoclax (ABT-263) and luspatercept-aamt (Reblozyl) are options for possible combinations for patients with myelofibrosis, as well as fedratinib (Inrebic) and ruxolitinib (Jakafi), 2 other JAK inhibitors. He believes that optimizing JAK inhibition and complimentary drugs will be something to look forward to in the future of this setting.

<< View more resources and information regarding myeloproliferative neoplasms

Ruben Mesa, MD, discusses the role of JAK inhibitors, which are currently being investigated in patients with myelofibrosis. He also spoke to what the future of this treatment landscape may be.

Investigators Study JAK Inhibitors in Patients With Myelofibrosis

Ruben Mesa, MD, director of the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, discusses the current challenges in the treatment landscape for researchers treating myelofibrosis (MF) and how a greater understanding of why patients relapse will help investigators overcome these challenges.

There are many challenges that still remain, Mesa says. There are therapies for patients with MF that are active, but they are not curative. Investigators aim to better deepen and lengthen the responses with treatment, and they have been largely looking at single agents and what combinations can create incremental benefit.

Mesa says we still do not fully understand why patients with MF progress, but once that is understood, we will be in a better situation to monitor any surrogate endpoints in terms of smaller studies and helping to sort through what can also be a very busy field of second-line studies. We can also aim to improve the progression-free survival rate among patients with myelofibrosis.

Ruben Mesa, MD, discusses the current challenges in the treatment landscape for researchers treating myelofibrosis (MF) and how a greater understanding of why patients relapse will help investigators overcome these challenges.

Challenges Remain in the Treatment Landscape for Myelofibrosis

Ruben Mesa, MD, the director of the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, discusses the role of ruxolitinib (Jakafi) and fedratinib (Inrebic), first-generation JAK inhibitors, as treatment of patients with myelofibrosis (MF).

Both fedratinib and ruxolitinib are available as frontline agents for patients with MF. In this setting, both drugs have shown to have the ability to improve splenomegaly and symptoms in patients with intermediate- and advanced-risk disease, says Mesa.

Additionally, investigators believe there is a likelihood to improve and extend survival with these agents in patients with MF with less debilitation. In addition, there may also be long-term effects in patients with bone marrow histologic features, as well as more subtle evidence of disease modification.

Ruben Mesa, MD, discusses the role of ruxolitinib and fedratinib, first-generation JAK inhibitors, as treatment of patients with myelofibrosis.

Fedratinib and Ruxolitinib Improve Survival as Treatment of Myelofibrosis

Ruben Mesa, MD, director of the Mays Cancer Center, home to UT Health San Antonio MD Anderson Cancer Center, discusses the current state of the treatment landscape for patients with myeloproliferative neoplasms (MPNs).

Mesa says this is an exciting time for the treatment of patients with MPNs, particularly in patients with essential thrombocytopenia and polycythemia vera after data were presented at the 2019 American Society of Hematology Meeting. Long-acting interferons continue to play a role in this space and are superior to hydroxyurea in both the first- and second-line settings.

In terms of myelofibrosis, a number of robust therapies are under development, including novel combinations of JAK inhibitors, Mesa says. BET inhibitors, TGF-beta inhibitors, LSD1 inhibitors, among others are under development for use both in combination and also as single-agents. Overall, this is an exciting time with a lot of new agents and treatment strategies under development, Mesa concludes. Hypomethylating agents and others are likely to have benefit for patients with advanced MPNs, as well, he says.

<< View more information from Ruben Mesa, MD

Ruben Mesa, MD, discusses the current state of the treatment landscape for patients with myeloproliferative neoplasms.

Highlighting Current Advances for the Treatment of Myeloproliferative Neoplasms

Ruben Mesa, MD, director of the Mays Cancer Center, UT Health San Antonio MD Anderson Cancer Center, gives advice on using the JAK inhibitors ruxolitinib (Jakafi) and fedratinib (Inrebic) in the community setting for patients with intermediate-risk myelofibrosis.

JAK inhibition is an alternative option and as such, it opens the door to improvements in outcomes. Mesa says this has been seen previously when multiple options became available in CML, MDS, and AML. The majority of patients diagnosed with myelofibrosis are already on therapy. Those patients who have a suboptimal response to their current treatment do not have many second-line options outside of clinical trials. Therefore, having an approved agent like ruxolitinib and fedratinib.

Ruben Mesa, MD, director of the Mays Cancer Center, UT Health San Antonio MD Anderson Cancer Center,&nbsp;gives advice on using the JAK inhibitors ruxolitinib and fedratinib in the community setting for patients with intermediate-risk myelofibrosis.<br />
&nbsp;

Ruben Mesa, MD | Authors

Articles

Treatment Approaches Become More Individualized as Field of Myelofibrosis Advances

Investigators Study JAK Inhibitors in Patients With Myelofibrosis

Challenges Remain in the Treatment Landscape for Myelofibrosis

Fedratinib and Ruxolitinib Improve Survival as Treatment of Myelofibrosis

Highlighting Current Advances for the Treatment of Myeloproliferative Neoplasms

Mesa Advises Community Oncologists on JAK Inhibitors for Intermediate-Risk Myelofibrosis