Ruben A. Mesa, MD, Professor of Medicine, Division of Hematology & Medical Oncology, Mayo Clinic, describes three phase II and phase III trials in myelofibrosis.

Pomalidomide will be compared to placebo to determine the true benefit of the drug for anemia. Pomalidomide may be active on its own or it may prove to be a natural complement to JAK2 inhibitor therapy, according to Mesa.

Another phase III study will examine the efficacy of SAR302503 in comparison to placebo.

Data from parallel phase II combination studies will examine ruxolitinib in combination with agents to help inhibit fibrosis, improve anemia, or target downstream pathways of JAK2.

New data and upcoming trial make it an exciting time for the treatment of myeloproliferative neoplasms, Mesa says.

Videos

Dr. Ruben Mesa on Late-Stage Trials in Myelofibrosis

Ruben A. Mesa, MD, Professor of Medicine, Division of Hematology & Medical Oncology, Mayo Clinic, discusses the long-term experience from the COMFORT-I and COMFORT-II trials in myelofibrosis.

Data from the COMFORT trials shows that most patients switched to ruxolitinib (from placebo or best alternative therapy). After the switch, patients saw benefits such as spleen size reduction and symptomatic improvement. These responses were durable as patients remained on ruxolitinib and experienced survival benefit.

Survival advantage was particularly noticeable in those who saw clear weight gain, reversible cachexia with the disease, and improvement in hypercholesterolemia.

Dr. Mesa on Long-Term Data From the COMFORT Trials

Ruben A. Mesa, MD, Professor of Medicine, Division of Hematology & Medical Oncology, Mayo Clinic, discusses the use of JAK2 inhibitors in patients with myelofibrosis.

Ruxolitinib, as well as several other agents, have been tested in patients with advanced myelofibrosis who are symptomatic and at high risk. Currently, ruxolitinib is approved for use in this population and has shown efficacy to decrease spleen size, minimize symptoms, and likely provide a survival advantage. Mesa believes that phase III trials analyzing pacritinib, CYT387, and SAR302503, will show benefit in the same population.

The question remains, Mesa says, as to whether or not JAK2 inhibitors could show benefit earlier in treatment to help prevent disease progression and if potential improvement to anemia is possible.

With regard to early-stage disease, phase III studies in polycythemia vera are ongoing based on phase II data, which demonstrated ruxolitinib was beneficial for improving symptoms, decreasing need for phlebotomies, and preventing vascular events. Mesa expects that there will be a role for JAK2 inhibitors in polycythemia vera, particularly in patients with problematic disease. Mesa concludes by noting that the path for JAK2 inhibitors in myelofibrosis is clear, while in polycthemia vera and essential thrombocythemia the path is evolving.

Dr. Mesa on the Role of JAK2 Inhibitors in Myelofibrosis

Ruben A. Mesa, MD, Professor of Medicine, Chair, Division of Hematology & Medical Oncology, Mayo Clinic, Arizona, discusses the phase III Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment (COMFORT) trials, which led to the FDA approval of ruxolitinib (Jakafi) for patients with myelofibrosis.

COMFORT-I was a placebo controlled studied that randomized patients 1:1 to receive either ruxolitinib or placebo. This trial enrolled patients in Australia and North America. The second trial, COMFORT-II, was conducted in Europe and randomized patients 2:1 to receive either ruxolitinib or best available therapy. In general, this resulted in most patients receiving hydroxyurea or glucocorticoids. Combined, the trials evaluated 528 patients.

In both trials ruxolitinib was greatly superior at improving splenomegaly, the swelling of the spleen associated with myelofibrosis. Only 1 patient receiving the placebo and none with best available therapy experienced a reduction in spleen size. Patients on both trials accomplished a marked reduction in disease-related symptoms and an improvement in quality of life.

Dr. Ruben Mesa, from Mayo Clinic, Arizona, Discusses the COMFORT Ruxolitinib Trials

Dr. Mesa Discusses the COMFORT Ruxolitinib Trials

Ruben A. Mesa, MD, Professor of Medicine, Chair, Division of Hematology & Medical Oncology, Mayo Clinic, Arizona, discusses the success of JAK1 and JAK2 inhibitors for the treatment of patients with myelofibrosis, a disease in which the bone marrow is replaced by fibrous scar tissue.

Inhibiting JAK pathways allows physicians to better manage the side effects associated with myelofibrosis. Prior treatment options, such as transplants, had only been slightly effective at easing symptoms. The recently approved agent ruxolitinib (Jakafi), an oral JAK1 and JAK2 inhibitor, was the first agent approved specifically to treat patients with myelofibrosis and has helped reduce the symptoms of the disease.

Many different JAK inhibitors are currently under investigation. Other agents being investigated include SAR302503, which is currently in phase III studies, and the agents CYT387 and SB1518 that are both in phase II studies.

JAK inhibiting agents have been very effective at improving splenomegalia, a serious side effect that can cause morbidity or mortality. These targeted agents have eased many of the symptoms associated with myelofibrosis, such as feeling tired, night sweats, anemia, and bone pain.

Dr. Ruben Mesa from the Mayo Clinic in Arizona Discusses JAK Inhibitors for Myelofibrosis

Ruben A. Mesa, MD

Articles

Dr. Ruben Mesa on Late-Stage Trials in Myelofibrosis

Dr. Mesa on Long-Term Data From the COMFORT Trials

Dr. Mesa on the Role of JAK2 Inhibitors in Myelofibrosis

Dr. Mesa Discusses the COMFORT Ruxolitinib Trials

Dr. Mesa Discusses JAK Inhibitors for Myelofibrosis