MPN News from 2022 ASCO
A number of important findings regarding MPNs were featured in June, at the 2022 American Society of Clinical Oncology (2022ASCO) Annual Meeting in Chicago. Some key highlights follow.
Rusfertide Shown to Reduce Phlebotomy
“The target in treating patients with PV (polycythemia vera) is to chronically maintain adequate hematocrit levels below 45 percent, which reduces the risk of thrombosis,” explains Ronald Hoffman, MD, of Tisch Cancer Institute, Mount Sinai. Phlebotomy – the periodic “letting” of blood to reduce red cell volume – is often the only means to that end.
“Most patients with PV are severely iron deficient, either due to their underlying disease or repeated phlebotomies,” according to Dr. Hoffman, who presented at 2022ASCO on two phase 2 studies of rusfertide treatment in phlebotomy-dependent PV patients. Anemia is the major contributor to the hallmark fatigue reported by PV and other MPN patients.
In the studies, patients showed normalization of iron deficiency, serum ferritin, and mean corpuscular volume (MCV), a value associated with the size of red blood cells.
Rusfertide was shown to maintain target hematocrit levels < 45 percent, which measures the proportion of red cells in a person’s blood. Meeting this target reduced or eliminated the need for phlebotomy, associated with varying hematocrit levels and contributing to anemia. In addition to the decreased risk of thrombosis (blood clots), patients benefitted from a reduced symptom burden.
“There was improvement in systemic symptoms associated with the administration of this drug,” according to Dr. Hoffman, “specifically in the impairment of intellectual capacity, so called brain fog, which has been quite impressive actually.”
With side effects primarily limited to the local injection site, Dr. Hoffman and colleagues are more than hopeful about the potential therapeutic reach of rusfertide in PV.
“The data is really very clean,” he says. “I think it would make an important contribution, essentially freeing these people up from the burdens of coming to the office frequently, getting phlebotomy . . . while hopefully continuing to improve their systemic symptoms. And I would anticipate that they would not require as close follow-up to make sure they meet their target and management levels.”
Phase 3 of the rusfertide trial is currently recruiting. Trial details HERE.
Dr. Hoffman is one of a distinguished international group of academic advisors for the MPNRF’s MPN Interferon Initiative.
MOMENTUM Study Phase 3 Promising for Myelofibrosis
“This study was designed specifically to highlight a select group of individuals for whom there is a significant unmet need,” according to Ruben Mesa, MD, Mays Cancer Center, UT Health San Antonio MD Anderson, who presented an update at 2022ASCO on the phase 3 randomized study of momelotinib versus danazol. Specifically, the trial is looking at symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor.
“It was superior to arguably our best alternative therapy for these patients (danazol),” he said. “Momelotinib was superior in terms of improvement in symptoms, and superior in terms of being transfusion free.”
Momelotinib proved to be a significantly better option than danazol for patients with a combination of splenomegaly (enlarged spleen), anemia, and other symptoms, and also for patients with thrombocytopenia.
The primary end point of the trial was a 50 percent or greater improvement in Total Symptom Score (TSS) after 24 weeks. Secondary end points were transfusion independence and a reduction of the spleen by at least 35 percent. A number of patients crossed over to the momelotinib arm at the end of 24 weeks on Danazol.
Findings from the study of 195 patients across 21 countries suggest that momelotinib represents a promising treatment approach to MF with anemia, or for patients with MF who may progress to symptomatic anemia.
FDA approval of momelotinib for use in the treatment of myelofibrosis was filed 10 days after this ASCO presentation.
Dr. Mesa has been awarded multiple grants by the MPNRF since 2003, including toward the creation of the practice changing MPN Symptom Assessment Form.
Navtemadlin for MPN Progression to AML
A poster session at 2022 ASCO led by Raajit Rampal, MD, PhD, Memorial Sloan Kettering Cancer Center, presented findings of an open-label, multicenter, phase 1b/2 study of navtemadlin (KRT-232) for patients with relapsed/refractory acute myeloid leukemia (AML) secondary to MPN.
This patient group has limited treatment options, resulting in poor prognosis. Although conventional AML therapy can induce responses in a subset of patients, it does not prolong survival in AML secondary to MPN, according to the authors. They suggest that these studies provide biological and clinical support for evaluating navtemadlin in this patient population. This trial is ongoing and will enroll patients at 65 global sites. Trial details HERE.
Dr. Rampal is a medical advisor for the MPN Research Foundation.