Ruben Mesa, MD

Ruben Mesa, MD, director of the UT Health San Antonio MD Anderson Cancer Center, discusses the COMFORT studies that demonstrated how ruxolitinib became a standard of care for patients with myelofibrosis.

In the COMFORT-I trial (NCT00952289), patients experienced improvements in their individual myelofibrosis-related symptoms, and most patients treated with ruxolitinib experienced a total symptom score (TSS) of 50% or greater. Moreover, patient reported outcomes showed that these patients self-reported their condition as either “much improved” or “very much improved” based on the Patient Global Impression of Change scale. Spleen volume reduction was also associated with these responses.

In the COMFORT-II study (NCT00934544), long-term findings showed that 53.4% of patients in the ruxolitinib arm of the study achieved a 35% or greater reduction in spleen volume at any time with a 0.48 (95% CI, 0.35-0.60) probability of maintaining their response at 5 years. In comparison, no patients on the best available therapy arm had a decrease in spleen volume at week 48 in the study compared with 28% of patients on ruxolitinib (

Mesa also discusses the results of a pooled analysis of the COMFORT trials that showed patients on ruxolitinib had a longer-term overall survival (OS) compared with other therapies at a median of 3 years of follow-up (HR, 0.65; 95% CI, 0.46-0.90; 

 = .01). An estimated OS at week 144 of treatment also showed stronger results for patients of ruxolitinib at 78%.

The main studies that led to the use of ruxolitinib [for patients with] myelofibrosis goes back to the COMFORT studies, the COMFORT-I and the COMFORT-II studies. In the COMFORT-I study, ruxolitinib was compared against placebo, with primary end points for improvement of splenomegaly and symptoms. In COMFORT-II, a parallel study done in Europe, the same end points with a comparator arm of best alternative therapy [were assessed]. With each of these studies, we saw the ruxolitinib was vastly superior to both control groups for improvements in splenomegaly and symptoms.

Over time, we've also seen that there's a strong signal that use of ruxolitinib leads to an improvement in survival, both with long-term analysis of a pooled analysis of both the COMFORT studies as well as real world evidence that has come out from the use of ruxolitinib. So, it really has become the cornerstone of therapy for myelofibrosis. [It has] now been approved a little over 10 years, whether alone or, as the field continues to evolve, with potential combinations.

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Ruben Mesa, MD, discusses crucial data from the COMFORT studies that show ruxolitinib's benefit in patients with myelofibrosis. 

Data Shows How Ruxolitinib is the Cornerstone of Treatment in Myelofibrosis

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.

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.

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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.

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

Ruben Mesa, MD | Authors

Articles

Data Shows How Ruxolitinib is the Cornerstone of Treatment in Myelofibrosis

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