ASH 2018 News : Episode 7

Dr. Mesa Discusses Exciting Abstracts on Myeloproliferative Neoplasms

Video

Ruben Mesa, MD, director of the UT Health San Antonio MD Anderson Cancer Center, discusses exciting abstracts on myeloproliferative neoplasms (MPNs) presented at the 2018 ASH Annual Meeting.

Several abstracts highlight the importance of acknowledging and understanding the relevance of molecular mutations in disease biology, progression, and targets for patients with MPNs, says Mesa. Longstanding debate over frontline therapy for patients with polycythemia vera (PV) or high-risk essential thrombocythemia prompted the launch of the phase III MPN-RC 112 trial. In the trial, patients were randomized to receive either pegylated interferon alfa-2a or hydroxyurea. Results indicated noninferiority between arms. Symptomatic improvement was observed in both arms. Although low-grade toxicities were observed with pegylated interferon alfa, the trial validates the safety and efficacy of this approach.

Additionally, 156-week follow-up data from the phase III RESPONSE-2 trial in PV were also presented. In the initial RESPONSE trial, patients with difficult disease had to have failed hydroxyurea and experience splenomegaly in order to receive ruxolitinib (Jakafi). RESPONSE-2 was created to acknowledge the patients with difficult disease who do not experience splenomegaly. Results demonstrated that these patients do just as well with ruxolitinib in terms of efficacy and durability.

The JAK inhibitor space continues to evolve with the emergence of pacritinib, fedratinib, and momelotinib. Pacritinib is currently being evaluated in the PAC-203 trial to identify the minimally effective dose for patients with myelofibrosis (MF). Physicians are hopeful that this will soon become available for patients with difficult MF. Now that the clinical hold on fedratinib has lifted, the inhibitor is on track for regulatory approval. A soon-to-open registration trial will add to existing phase II/III data with the JAK2 inhibitor. Momelotinib is also seeking regulatory approval, following positive phase III data reported and published in the Journal of Clinical Oncology. Several combination studies of JAK inhibitors and hypomethylating agents are also underway. The next step will be to identify the agents with enough activity to be used off label or receive FDA approval.

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