Aaron Gerds, MD, assistant professor of medicine in the Hematology and Medical Oncology Department at the Cleveland Clinic Taussig Cancer Institute, discusses the design and safety analysis of a phase II trial of luspatercept in patients with myelofibrosis-associated anemia.

In the open-label phase II trial, patients with myelofibrosis-associated anemia received luspatercept. Patients were grouped according to their exposure to ruxolitinib (Jakafi) and transfusion-dependence, says Gerds.

In addition to evaluating the activity of the agent, investigators analyzed safety. The most common adverse events (AEs) reported in the trial included elevated blood pressure, diarrhea, and bone pain, the latter of which had been reported in prior studies done in patients with beta-thalassemia and myelodysplastic syndrome. No disease-related AEs led to death, and all cases of hypertension were able to be controlled medically, concludes Gerds.

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Dr. Gerds on Design and Safety Analysis of a Trial With Luspatercept in Myelofibrosis

Aaron Gerds, MD, assistant professor of medicine in the Hematology and Medical Oncology Department at the Cleveland Clinic Taussig Cancer Institute, discusses the state of treatment in myeloproliferative neoplasms (MPNs).

JAK/STAT inhibitors are the current staples of treatment in MPNs, says Gerds. Currently, 2 JAK inhibitors, ruxolitinib (Jakafi) and fedratinib (Inrebic), are FDA approved for use in the treatment of patients with myelofibrosis. Ruxolitinib is also indicated in polycythemia vera (PV).

Although these drugs have had a significant impact on patients’ lives, the field is eager to move forward with novel combinations. Now, these approved agents are going to be evaluated in combination with other drugs in an attempt to broaden their utility, concludes Gerds.

Dr. Gerds on the State of Treatment in MPNs

Aaron Gerds, MD, assistant professor of medicine in the Hematology and Medical Oncology Department at the Cleveland Clinic Taussig Cancer Institute, discusses results of a phase II trial examining the safety and efficacy of luspatercept as a treatment for anemia in patients with myelofibrosis.

Results from the trial were presented at the 2019 ASH Annual Meeting and showed that luspatercept is effective in treating anemia in patients with myeloma, despite the stringent criteria for the primary end point, says Gerds. Four groups of patients were examined in the trial, including those who were on and off ruxolitinib (Jakafi) and, within those 2 groups, some patients did not receive any transfusions while others are transfusion-dependent, says Gerds.

For patients not receiving transfusions, a 1.5-gram increase in their hemoglobin count over a baseline of 12 weeks was required to meet the primary end point of the trial. Even if a patient’s hemoglobin was at a 1.4 increase, they were considered a non-responder, explains Gerds.

Responses with the agent were observed in all cohorts of this study, but there was a higher response rate in patients who received ruxolitinib plus luspatercept. When a less stringent end point is used, such as an average hemoglobin increase of 1.5 grams over 12 weeks, or a 50% reduction in transfusion burden, the response rates were much higher for this more clinically applicable end point, concludes Gerds.

Aaron Gerds, MD, discusses results of a phase II trial examining the safety and efficacy of luspatercept as a treatment for anemia in patients with myelofibrosis.

Dr. Gerds on Luspatercept to Treat Anemia in Myelofibrosis

Aaron Gerds, MD, assistant professor of medicine in the Hematology and Medical Oncology Department at the Cleveland Clinic Taussig Cancer Institute, discusses the adverse event anemia in patients with myelofibrosis.

Anemia is a really big issue in myelofibrosis, says Gerds; it affects around 40% to 50% of patients with the disease at the time of presentation. Furthermore, the most common treatment for myelofibrosis, JAK inhibitors, can lead to even more anemia. In fact, roughly 25% of patients who receive JAK inhibitors will become anemic over time, according to Gerds.

Anemia causes various complications in patients, including alloantibodies, transfusion reactions, and iron overload, adds Gerds. Additionally, it is burdensome for the patient to go to the cancer center, undergo screening, wait for the blood, and receive a transfusion; this can greatly impact their quality of life, says Gerds. For these reasons, ongoing research efforts aim to target anemia in patients with myelofibrosis, concludes Gerds.

Aaron Gerds, MD, discusses the adverse event anemia in patients with myelofibrosis.

Dr. Gerds on Addressing Anemia in Myelofibrosis

Aaron Gerds, MD, discusses the future treatment of patients with myeloproliferative neoplasms (MPNs) through the use of JAK-STAT pathway.

The JAK inhibitors, fedratinib (Inrebic) and ruxolitinib (Jakafi), have recently been approved by the FDA for the treatment of patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera) myelofibrosis. Hydroxyurea has been a common therapy for patients with myelofibrosis and PV. For patients who have not responded to hydroxyurea, fedratinib and ruxolitinib offer a second-line therapy option.

The availability of fedratinib and ruxolitinib in the MPN treatment landscape will serve as the backbone of future research, Gerds concludes.

Aaron Gerds, MD, discusses the future treatment of patients with myeloproliferative neoplasms through the use of JAK-STAT pathway.

Aaron Gerds, MD

Articles

Dr. Gerds on Design and Safety Analysis of a Trial With Luspatercept in Myelofibrosis

Dr. Gerds on the State of Treatment in MPNs

Dr. Gerds on Luspatercept to Treat Anemia in Myelofibrosis

Dr. Gerds on Addressing Anemia in Myelofibrosis

Dr. Gerds on Future Treatment of Patients With Myeloproliferative Neoplasms