Novel Advances in the Treatment of Patients With Myelofibrosis

At the 2023 Lymphoma, Leukemia & Myeloma Congress in New York, Ruben Mesa, MD, FACP, Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Charlette, North Carolina, discusses evolutions in the treatment landscape for patients with myelofibrosis (MF). 

Transcript:

Hello, my name is Ruben Mesa, and I'm the Executive Director of the Atrium Health Wake Forest Baptist Comprehensive Cancer Center. I'm so excited to be here at the Lymphoma, Leukemia & Myeloma Congress here in New York on a beautiful fall day and having the opportunity to update those attending on myelofibrosis. 

Myelofibrosis, [which is] a chronic myeloproliferative neoplasm, has been transformational in the amount of additional understanding we've had regarding the biology of the disease, particularly with the driver mutations in JAK2, CALR and MPL.

First, I'll be updating the attendees on our 4 FDA approved therapies. We've had ruxolitinib approved since 2011, which has been very impactful for splenomegaly symptoms and has had a survival advantage for patients with myelofibrosis. The unmet needs include improvement in anemia, challenges with patients with thrombocytopenia; Still a finite benefit that is obtained, but very real.

Second, fedratinib, [which was] approved in 2019, overlaps significantly with the efficacy of ruxolitinib, which is a good thing. [It is] helpful in the second-line setting, but does still have some of the same limitations regarding anemia, thrombocytopenia including additional things we watch for in terms of thiamine levels with a black box warning as well as GI side effects.

Pacritinib, approved in 2022, is particularly helpful for those individuals with thrombocytopenia. There truly is no lower level of platelets that is necessary for considering pacritinib. So, it has a broad indication for individuals with a platelet count of less than 50,000. [It is] helpful at any platelet level, but that's really its niche. Also, between 50,000 to 100,000 is a clear consideration.

The [most recent] approval is of momelotinib in September of 2023, [with a] broad indication for patients with myelofibrosis with anemia. It's a JAK inhibitor, and can improve spleen and symptoms, but can also help to improve anemia for a range of reasons; the inhibition of AcV1, decreases in hepcidin. Truly, it is a powerful addition to the armamentarium and really can be considered in the frontline and second-line setting.

Second, we'll be discussing a range of things in development. I think from these 4 JAK inhibitors, we really pivot toward combination approaches. Multiple upcoming phase 3 trials are [going to focus] in the frontline and second-line setting[s] with pelabresib and ruxolitinib, with navitoclax and ruxolitinib, with imetelstat, and many other agents in development.

This is a very exciting time in myelofibrosis treatment. Before 2011, we had zero drugs approved for myelofibrosis. Increasingly, I think we'll have more individualized approaches based on the patient's phenotype, based on their blood counts, and potentially on molecular markers. We look for further and deepening disease course modification as these therapies evolve.

Source:

Mesa R. Updates in the Management of Myelofibrosis. Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-21, 2023. New York, NY