Researchers from UCLA Jonsson Comprehensive Cancer Center and UCLA Health will participate in dozens of presentations at the annual meeting of the American Society of Hematology (ASH), held virtually and in person in Atlanta Dec. 11-14. A few of these are highlighted below.
(Embargoed until Dec. 14 at 8:45 a.m. EST)
Elizabeta Nemeth, PhD, a professor of medicine at the David Geffen School of Medicine at UCLA, and director of the UCLA Center for Iron Disorders, will receive the William Dameshek Prize for contributions to the understanding of iron homeostasis, as announced earlier this year.
The award presentation will be Tuesday, Dec. 14, at 8:45 a.m. EST during the American Society of Hematology Annual Meeting and Exposition. The programs are virtual and in person in Atlanta.
According to ASH, “Dr. Nemeth’s work helped define the role of the iron-regulatory hormone hepcidin in different iron disorders including hereditary hemochromatosis, β-thalassemia and anemia of inflammation, elucidated the mechanism of action of hepcidin, and developed novel hepcidin-targeted candidates for the treatment of iron disorders. Dr. Nemeth described how mechanisms limiting iron availability to invading pathogens are crucial in defending against infection, and that those same mechanisms are responsible for the development of anemia in many chronic inflammatory conditions.”
Nemeth is president-elect of the International BioIron Society and Associate Editor for the American Journal of Hematology. She helped start three biotechnology companies focused on iron-related diagnostics and therapeutics.
The William Dameshek Prize, named for the late Dr. William Dameshek, a past president of ASH and the original editor of Blood, recognizes an early- or mid-career individual who has made a recent outstanding contribution to the field of hematology.
Nemeth also will co-moderate an ASH session: Iron Homeostasis and Biology: Disorders of Iron and Heme and Novel Treatments. The session, co-moderated by Dr. Karin E. Finberg, Yale School of Medicine, will be Monday, Dec. 13, from 4:30 to 6 p.m. (Embargoed until this time.)
Program: Oral and Poster Abstracts
Poster III
Monday, December 13, 2021, 6:00 PM EST (Embargoed until this time.)
Dr. Gary Schiller, a professor of hematology/oncology at the UCLA Health Jonsson Comprehensive Cancer Center and director of the hematological malignancies/stem cell transplantation unit, will provide an update on efforts to improve treatment for relapsed or refractory acute myeloid leukemia (AML), the most common acute leukemia in adults. Because many newly diagnosed patients are too elderly or unhealthy to undergo standard first-line treatment – aggressive chemotherapy – options often have been limited.
Venetoclax, which inhibits B-cell lymphoma-2 (BCL-2) proteins, has been used successfully against chronic lymphocytic leukemia and has shown limited promise in treating acute lymphocytic leukemia. However, because AML also expresses other, related proteins that are not well targeted by venetoclax, this treatment alone often results in relapse or refractory disease. Therefore, researchers and clinicians seek combination strategies that will work synergistically to kill cancer cells.
In this multicenter study, led by Schiller, researchers are studying a strategy to enhance the potency of venetoclax by combining the treatment with targeted radiotherapy to damage the cancer’s DNA. Lintuzumab-Ac225, a monoclonal antibody radioconjugate, is highly toxic to tumor cells, targeting CD33, a cell-surface antigen expressed on most AML cells.
The Phase I dose-escalation study was designed to determine maximum tolerated dose of lintuzumab-Ac225 when given in combination with venetoclax. Schiller and colleagues report that in preliminary data, the combined therapies have an acceptable clinical safety profile, supporting further evaluation in patients with relapsed or refractory AML. Schiller said a 67% overall response rate in patients with a mutation of the TP53 tumor suppressor gene – one of the most frequently mutated genes in cancer – is especially encouraging. A Phase II study will assess recommended dose and best overall response up to six months after starting treatment.
Program: Oral and Poster Abstracts
Poster I
Saturday, December 11, 2021, 5:30 PM EST (Embargoed until this time.)
Anemia affects 30% to 40% of patients with moderate-to-advanced non-dialysis-dependent chronic kidney disease, according to estimates. Treatment has traditionally included iron supplementation and blood transfusion, but more recently, the administration of erythropoiesis-stimulating agents (ESAs) by injection have been used to increase production of red blood cells. However, these interventions – like transfusions – have significant safety risks.
Roxadustat is a new oral drug – the first small-molecule HIF-PHD inhibitor – designed to enhance synthesis of the hormone erythropoietin and improve iron bioavailability. Although it is in use in other countries, it is not approved by the U.S. Food and Drug Administration.
Dr. Anjay Rastogi, professor and clinical chief of nephrology at the David Geffen School of Medicine at UCLA, with colleagues in Australia, the United Kingdom and Sweden, conducted a pooled post-hoc analysis of several Phase III trials to evaluate the effects of Roxadustat. They looked at selected baseline hemoglobin values, and among results they will present at ASH, found that Roxadustat improved anemia versus placebo across all baseline hemoglobin values studied.
Program: Friday Satellite Symposia
Friday, December 10, 2021: 7:00 PM EST (Embargoed until this time.)
Dr. John Glaspy, a hematologist/oncologist and professor of medicine at the UCLA Health Jonsson Comprehensive Cancer Center, will be one of four featured speakers on cancer-related anemia treatment. The program will be chaired by Dr. George M. Rodgers of the University of Utah, and Glaspy will be joined by Dr. Patricia A. Locantore-Ford, University of Pennsylvania, Penn Medicine; Dr. Thomas G. Deloughery, Oregon Health and Science University; and Dr. Michael Auerbach, Auerbach Hematology-Oncology Associates Inc.
Glaspy is co-chair of the Division of Hematology/Oncology at the David Geffen School of Medicine at UCLA. He is the director of the UCLA Jonsson Comprehensive Cancer Center Clinical Research Unit and the Women’s Cancer Research Program. He is involved in basic research in tumor immunology and the effects of fatty acids on carcinogenesis. His clinical interests include chemotherapy-induced anemia, the role of hematopoietic growth factors in cancer management, and new approaches to the treatment of breast cancer and malignant melanoma.
Attendees will have the opportunity to interact with the expert faculty on all aspects of cancer-related anemia, including chemotherapy-induced anemia. According to the ASH abstract: “The session will begin with a review of iron metabolism and absorption, including the distinctions between absolute and functional iron deficiency, and the impact of those distinctions on treatment decisions. An appraisal of the etiology and foundational pathophysiology of CRA will follow, with a central emphasis on the role of hepcidin and functional iron deficiency (FID) in a hyperinflammatory disease state like cancer, and how those processes should lead to preferential use of intravenous (IV) iron versus oral iron in patients with cancer. Completed and ongoing clinical trials of IV iron for CRA will be examined, and next generation formulations with nanocolloidal drug design will be highlighted, especially their improved safety profiles. Finally, using real-world patient cases, hematology/oncology experts will share insights on how and why IV iron possesses the capacity to revolutionize treatment of CRA and CIA.”
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