New Drug Approvals and Looking Forward

EP: 1.Defining Myeloproliferative Neoplasms

EP: 2.Therapeutic Options for Patients With MPN

EP: 3.The Role of JAK2 in MPNs

EP: 4.Disease Progression in MPN

EP: 5.Targeted Therapies for Essential Thrombocythemia

EP: 6.Individualized Therapy for Low- and High-Risk Patients With MF

EP: 7.Targeted Therapies for Polycythemia Vera

EP: 8.Targeted Therapies for Myelofibrosis

EP: 9.Alternative Dosing and JAK Inhibitors in the Second-Line Setting

EP: 10.Ongoing Studies and Combination Therapy in MPNs

EP: 11.Managing Withdrawal Syndrome and Rechallenging

Now Viewing

EP: 12.New Drug Approvals and Looking Forward

EP: 13.Searching for a Cure for MPNs

Srdan Verstovsek, MD: The last topic is the last JAK inhibitor out there, and it may be approved, we will see later this year. This is pacritinib, a JAK inhibitor that is not that myelosuppressive at all. The dose-limiting toxicity in the studies with pacritinib is GI [gastrointestinal]—nausea, vomiting, and diarrhea—as problematic. It is not at a high grade, but it is common enough not to escalate the dose. It appears, therefore, that it is less myelosuppressive, and it can be given to patients with low platelet counts, below 50,000/μL. I think if this is approved—and we hear that the application for its approval is under review by the FDA—that will have a significant role for patients with platelets below 50,000/μL, who struggle.

Andrew Kuykendall, MD: Yes, we have talked about how we can safely dose ruxolitinib and fedratinib for patients who have low platelets, but we are talking about 50,000 to 100,000/μL. Now we are talking about the ability to give an agent that has led to significant responses for patients with platelets even lower than that. We really do not have options for that patient population. We try to very gently provide ruxolitinib in some cases because we have nothing else to give, or we are giving doses that we do not think are clinically that relevant. Sometimes, we are reaching for things like hypomethylating agents, frankly, for patients with low platelets, and those cause their own toxicity that can be quite a challenge. This could be a game changer for a patient population that has had very few options.

Srdan Verstovsek, MD: I agree. We are looking first at the frontline and the second-line setting, but then we are separating patients based on their characteristics. In the front line, that group would be patients with platelets below 50,000/μL. We cannot do much there—there are bad outcomes, a poor prognosis, bad anemia, thrombocytopenia. They are usually tied to each other and life is short. Then, in the second line, again a separation with fedratinib perhaps in 1 corner with the spleen and symptoms, momelotinib possibly for anemia and symptoms, pacritinib for patients with low platelets. We are branching out, and on top of this, we are exploring combinations in the front line. There will be combinations, I am sure, in the second line in due time, and then the anemia drugs will complement the JAK inhibitors in enhancing the production of red blood cells and make it easier for us to guide the treatment of patients with the JAK inhibitors that are myelosuppressive.

I think the spectrum over the next 3 to 5 years, because we have so many phase 3 studies, there are about 10 or 11 phase 3 studies underway, exploring all the news with different combinations or single-agent drugs. In 3 to 5 years, we will have a difficult task to perhaps put together an algorithm to help decide what to do. It will be still individualized. No patient is the same, because all these problems that exist do not exist in isolation. Not all platelets exist with a big spleen, or may or may not exist with the anemia, or anemia may be in isolation from the others. There will be still a lot of learning how to optimally use those medications if they become available in the next 3 to 5 years.

I think the future for us in therapy for patients with myelofibrosis is quite good. If we have, let’s say, half of these phase 3 studies being successful, we will be right there, discussing how to stack up the therapies and eventually, hopefully, prolonging the lives of these patients with all these options.

Transcript edited for clarity.