Dr Palandri on Efforts to Elucidate the Role of Predictive Markers for Ruxolitinib in Myelofibrosis

"In the future, I hope that we can have an integrated model sharing clinical and molecular parameters in order to guide our treatment decisions. The implementation of molecular findings over time could be a step forward in our understanding of [this] disease and also in optimizing the management of myelofibrosis."

Francesca Palandri, MD, an adjunct professor in the Department of Medical and Surgical Sciences at the University of Bologna in Italy, discussed additional research that could elucidate the role of predictive markers for ruxolitinib (Jakafi) response in myelofibrosis, alongside other clinical parameters.

In myelofibrosis, a critical need remains for a more comprehensive and integrated approach to evaluating for clinical predictors of response with ruxolitinib based on individual disease phenotypes, Palandri began. She stressed the importance of addressing and influencing physician attitude, aiming to stimulate a correct and timely use of ruxolitinib to ensure patients receive this therapy at optimal stages of their disease course. Beyond these clinical and behavioral factors, it is imperative to continuously implement knowledge of the biological characteristics of a disease, Palandri underscored. Looking to the future, Palandri expressed a strong hope for the development of an integrated model that effectively combines clinical parameters and molecular parameters to guide treatment decisions. This approach would lead to more personalized and effective therapeutic strategies for improved patient outcomes, Palandri stated.

Another critical aspect of research in myelofibrosis is the ability to assess the dynamics of a disease over time, Palandri continued. She pointed to the significant utility of established prognostic models, specifically noting the recent integration of a prognostic model of response with ruxolitinib. This model may be very important to evaluate the dynamics of a disease over the first 6 months of therapy, Palandri noted. Identifying patients who may experience poor prognosis allows for more timely intervention or adjustment of therapy to mitigate adverse outcomes, she said. Overall, the implementation of molecular findings over time could be a step forward in understanding the disease and optimizing the management of myelofibrosis, Palandri concluded.

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Francesca Palandri, MD, discusses research needed to clarify the role of predictive markers for ruxolitinib response in myelofibrosis.
 

Dr Palandri on Outcomes With Momelotinib in Myelofibrosis Per Dual SVR35 and Transfusion Independence

"We observed that the dual response was significantly higher for the patients treated with momelotinib vs ruxolitinib. This is important because…we saw that for patients achieving a transfusion independence response with or without a spleen response, their prognosis was much better."

Francesca Palandri, MD, adjunct professor in the Department of Medical and Surgical Sciences at the University of Bologna, discussed findings from a subgroup analysis of the phase 3 SIMPLIFY-I trial (NCT01969838), which assessed how dual spleen response and transfusion independence (TI) correlate with improved prognosis after treatment with momelotinib (Ojjaara) in JAK inhibitor–naive patients with myelofibrosis and anemia.

The post hoc analysis focused on the subset of JAK inhibitor–naive patients with baseline hemoglobin less than 10 g/dL, reflecting the real-world population for whom momelotinib would be most relevant, Palandri began.

SIMPLIFY-I was a randomized trial comparing momelotinib (n = 215) vs ruxolitinib (n = 217) in patients with intermediate- or high-risk myelofibrosis. This analysis evaluated spleen volume reduction of at least 35% (SVR35), TI, and dual response (SVR35+TI) at week 24 across subgroups stratified by key baseline features, including platelet count.

Palandri noted that patients treated with momelotinib were more likely to achieve a dual response compared with those receiving ruxolitinib, particularly in patients with baseline platelet counts of less than 200 x 10⁹/L. Importantly, the dual response benefit with momelotinib was also observed in patients with platelet counts of 200 x 10⁹/L or higher, she noted. In these cases, although ruxolitinib maintained spleen response activity, it was associated with greater hematologic toxicity and a higher need for transfusions, resulting in lower dual response rates overall, Palandri explained.

The clinical significance of this dual response was underscored by subsequent analyses correlating response status with survival outcomes, Palandri continued. Patients who achieved transfusion independence—whether or not they also achieved a spleen response—demonstrated improved overall survival compared with those who did not. These findings support the prognostic value of early treatment response at 24 weeks, particularly regarding anemia control, she reiterated.

According to Palandri, these data reinforce the importance of targeting both spleen burden and transfusion dependency in the management of myelofibrosis. Momelotinib's ability to deliver dual clinical benefits may translate to improved long-term outcomes in patients with baseline anemia, making it a relevant therapeutic option for this population, she concluded.

Francesca Palandri, MD, shares SVR35 rates with momelotinib vs ruxolitinib across patient subgroups in the anemic subpopulation of SIMPLIFY-1.

Francesca Palandri, MD

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Dr Palandri on Efforts to Elucidate the Role of Predictive Markers for Ruxolitinib in Myelofibrosis

Dr Palandri on Outcomes With Momelotinib in Myelofibrosis Per Dual SVR35 and Transfusion Independence