Selina Luger, MD

Speaking at the 2016 American Society of Hematology (ASH) Annual Meeting & Exposition, before the hold on pacritinib was lifted (in January 2017), Selina Luger, MD, of the University of Pennsylvania, Philadelphia, commented, “I think the U.S. Food and Drug Administration (FDA) needs to revisit its decision to put this drug on clinical hold. Pacritinib is good for patients with low platelet counts and has many of the benefits seen with prior therapies.” Dr. Luger was co-moderator of the session where pacritinib data were presented, but she was not involved in the study.

In PERSIST-1, pacritinib looked like it had some toxicity, continued Dr. Luger. “I think you have to realize that these patients have a disease...[that] is much more toxic than what we have seen with this drug. I would not give this drug to a healthy individual, but we need to learn how to minimize those toxicities in these sick patients,” she declared.

Stephanie Lee, MD

“PERSIST-2 is the only randomized trial to date in patients with myelofibrosis and thrombocytopenia and prior [Janus kinase 2] inhibitor exposure. This study is intriguing. Pacritinib did improve symptoms and spleen volume, but it remains to be seen what the FDA will do,” admitted Stephanie Lee, MD—again, before the clinical hold was removed. Dr. Lee, who is ASH Secretary, Professor at the University of Washington School of Medicine, and a member of the Fred Hutchinson Cancer Research Center in Seattle, was co-moderator of the ASH premeeting webinar.

Promising Research Areas

Also commenting on this study, Gabriela Hobbs, MD, of Massachusetts General Hospital, Boston, said: “It is commendable that these researchers included patients who are not typically included in clinical trials and were not included in the studies of ruxolitinib [Jakafi].”

Gabriela Hobbs, MD

That said, she would like to see more details about the adverse events that occurred in the trial. “Before I would use this drug, or even comment on whether the FDA should release the hold on it, I would like to have more data on the adverse events and the characteristics of the patients affected. Cardiac failure and intracranial hemorrhage are serious events, and I would like to have more information on the patients who experienced adverse events to help decide which patients are best suited for this therapy,” Dr. Hobbs admitted.

If the safety issues were better understood, pacritinib has the potential to play an important role in treating patients with myelofibrosis and thrombocytopenia, she continued. “Ruxolitinib does not help patients with low platelet counts. There is no cure for these patients, except for transplantation, and many people with myelofibrosis do not qualify for transplant due to older age or comorbidities.”

“The available treatments, including JAK1/2 inhibitors, do not modify the underlying biology of myelofibrosis,” Dr. Hobbs continued. “But I am hopeful, because there are promising areas of research, including combining a JAK1/2 inhibitor with other drugs, such as phosphoinositide 3-kinase–delta and hedgehog inhibitors, in addition to a variety of other agents that are being tested independently.” ■

Disclosure: Dr. Hobbs reported no potential conflicts of interest.