Dr Rampal on Personalizing Treatment Strategies for Patients With Myelofibrosis

“We’re fortunate to be in an era where we can be selective about the drugs we use [for patients with myelofibrosis].”

Raajit Rampal, MD, director of the Center for Hematologic Malignancies and director of the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, discussed considerations when selecting between available treatment options for patients with myelofibrosis.

The optimal treatment approach for a given patient depends on their symptom burden and profile, Rampal began by stating. For instance, patients with severe symptoms and an enlarged spleen may benefit from therapy with JAK inhibitors, such as ruxolitinib (Jakafi) or fedratinib (Inrebic), he said.

Notably, ruxolitinib was FDA approved in 2011 for the treatment of patients with intermediate- or high-risk myelofibrosis, including primary myelofibrosis and secondary myelofibrosis (post-polycythemia vera/post-essential thrombocythemia myelofibrosis). Ruxolitinib was the first agent to gain approval specifically for patients with this disease.

In 2019, the FDA approved fedratinib for the treatment of adult patients with intermediate-2 or high-risk primary or secondary myelofibrosis. This regulatory decision was supported by data from the phase 3 JAKARTA trial (NCT01437787), in which 37% of patients who received fedratinib at 400 mg (n = 96) achieved spleen volume reduction of at least 35% (SVR35) at the end of cycle 6 compared with 1% of those who received placebo (n = 96; P < .0001).

Conversely, patients who are highly anemic might experience better outcomes with momelotinib (Ojjaara), Rampal continued. Moreover, pacritinib (Vonjo) may be the most effective treatment option for patients with thrombocytopenia, he stated.

In 2022, the FDA granted accelerated approval to pacritinib for the treatment of adult patients with intermediate- or high-risk primary or secondary myelofibrosis with a platelet count below 50 × 10⁹/L. This regulatory decision was supported by data from the phase 3 PERSIST-2 trial (NCT02055781), in which patients with a baseline platelet count below 50 × 10⁹/L who received pacritinib at 200 mg achieved an SVR35 rate of 29%; this rate was 3% among patients who received placebo.

Most recently, in 2023, the FDA approved momelotinib for the treatment of adult patients with intermediate- or high-risk primary or secondary myelofibrosis with anemia. This regulatory decision was based on data from the 3 MOMENTUM trial (NCT04173494), in which 25% of patients who received momelotinib (n = 130) had a Myelofibrosis Symptom Assessment Form v4.0 total symptom score reduction of at least 50% vs 9% of those who received danazol (n = 65; P < .01).