Mesa Discusses Practice-Changing Presentations at ASH 2021 in Myelofibrosis

At ASH 2021, CancerNetwork® spoke with Ruben Mesa, MD, of UT Health San Antonio MD Anderson Cancer Center, about which presentation from the conference could be practice changing for patients with myelofibrosis.

Several key things [were presented] at ASH 2021. First a couple in the basic sciences, several discoveries as they relate to why patients with myelofibrosis might progress to acute myeloid leukemia, both with TP53 [mutations] and how that impacts the biology and inflammation in the bone marrow, a TP53 toxic environment, and higher risk of progressive disease as well as other molecular mutations such as DUSP6 in correlation with progression. Progression is an important [issue], it is longer term but impactful because it might impact which therapies are chosen and new therapies that are developed particularly for more advanced acute myeloid leukemia.

In terms of therapy for myelofibrosis, I would say that several things [could be practice changing], first with the combination therapies. [We have] more information regarding pelabresib. We have data that are suggesting important improvements with the combination therapy in patients with de novo disease who are JAK2 inhibitor naïve. We also saw very nice data for its use in the second-line setting in people who had failed ruxolitinib [Jakafi]. That concept of BET inhibition as a novel mechanism of action might be very impactful, either in combination or as second line therapy.

We saw several other mechanisms of action that clearly are active, including the drug tagraxofusp [Elzonris] which is approved in other disorders. It can improve spleen and symptoms in the second-line setting. [We also saw data for the] drug selinexor [Xpovio] with the AVID200, which works on TGF-β, that was a trial that we did through the Myeloproliferative Neoplasm Research Consortium. There were many different novel mechanisms of action, and some important other studies in development. There is a phase 3 study with a luspatercept (Reblozyl), that might help to improve anemia, in combination with ruxolitinib. It really is a theme [that we have these] JAK inhibitors, up to 4, and then several additional drugs with novel mechanisms of action that might have an impact alone in the second-line setting or in combination.