Transfusion Independence With Momelotinib Could Inform Treatment Decisions in Myelofibrosis

Article

The investigational JAK inhibitor momelotinib is effective at treating anemia in patients with myelofibrosis, resulting in improved rates of transfusion independence compared with ruxolitinib.

 Ruben A. Mesa, MD

Ruben A. Mesa, MD

The investigational JAK inhibitor momelotinib is effective at treating anemia in patients with myelofibrosis, resulting in improved rates of transfusion independence compared with ruxolitinib (Jakafi), said Ruben A. Mesa, MD, who added that understanding this benefit could inform treatment decisions for this patient population.1

“Indeed, as survival is being seen as a broader goal and end point in myelofibrosis studies, the ability to improve anemia is an important contribution in that assessment,” said Mesa.

Findings from subgroup analyses of the phase 3 Simplify 1 (NCT01969838) and Simplify 2 (NCT02101268) trials indicated that week-24 transfusion independence correlated with improved overall survival (OS) in patients treated with momelotinib (HR, 0.30; P = .0001). Moreover, higher rates of transfusion independence were observed with momelotinib vs ruxolitinib irrespective of the degrees of baseline anemia, baseline platelet count, or transfusion status.

Additionally, week-24 end points, including reduction in spleen volume and symptom improvements, demonstrated trends toward improved OS in responders; however, these trends were not statistically significant. 

In an interview with OncLive, Mesa, director of UT Health San Antonio MD Anderson Cancer Center, further discussed the results of these analyses and elaborated on the clinical implications of achieving transfusion independence in myelofibrosis.

OncLive®: How do these data regarding transfusion independence in myelofibrosis supplement the data regarding improved survival?

Mesa: Exciting developments [are emerging] in [the management of] myeloproliferative neoplasms [MPNs]. One relates to an abstract I presented [during the 2021 European Hematology Association Congress] is [regarding] the issue of survival.

We have had an increased signal that therapies [that are] beneficial for myelofibrosis affect survival. At the 2020 ASH Annual Meeting, [we saw] real-world evidence that the use of ruxolitinib over the past decade has led to improvements in survival. Those data built on other analyses that we have previously presented on long-term follow-up from the COMFORT studies [NCT00952289; NCT00934544].

At the 2021 EHA Meeting, [a lot of the data presented in MPNs were] all about survival. Further real-world evidence from additional groups [showcased] the effect of ruxolitinib [on] prolonging survival. Data with imetelstat, as well as fedratinib [Inrebic], also suggested improvements in survival.

The analysis that I presented related to momelotinib and the affect [of the agent] on transfusion independence.

The Simplify 1 and Simplify 2 studies were randomized trials of momelotinib, a JAK1/2 inhibitor. We had found that, in addition to improving splenomegaly and symptoms, [momelotinib] helped to improve anemia, perhaps through the mechanism of inhibition of ACVR1 or ALK2. [Momelotinib] helped to decrease hepcidin.

What methods were used to conduct these analyses?

In terms of methods, these were true prospectively conducted trials. Simplify 1 was a very large frontline study of momelotinib vs ruxolitinib in over 400 patients [with myelofibrosis]. Simplify 2 was a second-line study [of momelotinib] vs best available therapy, which could have included ruxolitinib even for those who had progressed on it.

Individuals were assessed in this analysis regarding transfusion-independent response, meaning no red [blood] cell transfusions for greater than 12 weeks with a hemoglobin of greater than 8. [They were also] assessed for spleen and symptom response.

What did the results demonstrate?

The main results showed that, in Simplify 1, the week-24 transfusion-independent responders randomized to momelotinib had an OS advantage. The 3-year survival rate was 80% [compared with] 50% in transfusion-independent non-responders, which was highly statistically significant. Additionally, in Simplify 2, there was a very strong trend toward improvement in survival in the transfusion-independent responder arm.

What are the potential clinical implications of these findings on treatment decisions in myelofibrosis?

[These data] demonstrate that the achievement of transfusion independence has a real correlation with improvement in survival.

It has previously been shown that anemia and transfusion dependence are both prognostically negative for patients with myelofibrosis. However, this is the first time [we have] demonstrated that if there is improvement in anemia and achievement of a transfusion-independence response, [there is a] correlation with improvement in survival. [These data] may have subsequent implications in terms of our treatment guidelines and algorithms if we then have multiple lines of therapy available that could impact anemia.

Reference

  1. Mesa RA, Oh ST, Gerds AT, et al. Transfusion independence is associated with improved overall survival in myelofibrosis patients receiving momelotinib. J Clin Oncol. 2021;39(suppl 15):7046. doi:10.1200/JCO.2021.39.15_suppl.7046
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