The 2024 ASH Annual Meeting showcased groundbreaking research across various hematologic disciplines. Here we highlight some of the most impactful oral presentations that have the potential to reshape clinical practice and deepen our understanding of hematologic diseases.
Old Meets New in the Fight Against Sickle Cell Disease
The “Golden Globules” for red cell disorders go to … Matthew M. Heeney, MD, and Abena Appiah-Kubi, MD, MPH.
Dr. Heeney presented initial results from the study of base-editing technology BEAM-101 — an investigational autologous cell therapy for sickle cell disease (SCD) that boosts fetal hemoglobin (HbF) production (Abstract 513). Traditional gene-editing technologies create DNA breaks, which may result in genomic instability and unintended mutations. The ex vivo base-editing technique employed in the phase I/II BEACON trial avoids reliance on DNA breaks. Early results from six patients (ages 19-27) showed successful treatment with no evidence of double-stranded DNA breaks. Patients were successfully mobilized with plerixafor and received a mean dose of 11.9 x 106 (5.2-23.4) viable CD34+ cells/kg after busulfan myeloablative conditioning. The data confirms the safety, tolerability, and efficacy of BEAM-101, with impressive HbF induction to more than 60% and no vaso-occlusive crises.
Meanwhile, hydroxyurea remains an “oldie but goodie,” a mainstay treatment option. Dr. Appiah-Kubi presented results from the Hydroxyuera Optimization Through Precision Study, which revealed a new way to dose hydroxyurea in young children, using pharmacokinetics to achieve the maximum tolerated dose more effectively and efficiently (Abstract 175). This strategy showed major hematologic improvements, with elevation in HbF levels from an average of 27 to 34%, confirming the feasibility of this approach.
Continued Innovation in Hemophilia Care
The Golden Globule for bleeding disorder management goes to … Tadashi Matsushita, MD, who presented the results of a study of new bimonthly subcutaneous prophylaxis by Mim8, a next-generation factor VIIIa mimetic for hemophilia A patients that showed excellent efficacy and safety in the current interim analysis of FRONTIER4 (Abstract 718). Compared to emicizumab, Mim8 has a monovalent anti factor IXa arm that stimulates the proteolytic activity needed to activate factor X.
Rewriting the Rules of Erythropoiesis
The Golden Globule for bone marrow failure syndromes goes to … Naomi Taylor, MD, who delved into the metabolic processes governing erythroid lineage commitment and terminal differentiation. Her presentation during the Presidential Symposium highlighted the importance of metabolite transporters and metabolic reprogramming in effective erythropoiesis. Dr. Taylor also explored the implications of isocitrate dehydrogenase mutations in myelodysplastic syndromes and sideroblastic anemia, suggesting that targeted metabolic interventions could revolutionize treatment strategies for these disorders.
Off-the-Shelf T-Cell Therapy to the Rescue
The Golden Globule for myelofibrosis goes to … Lucia Masarova, MD, who presented phase Ib data on CK0804, an allogeneic, off-the-shelf regulatory T cell (Treg) therapy candidate for myelofibrosis patients unresponsive to standard treatments (Abstract 999). The study demonstrated a favorable safety profile and encouraging efficacy signals, including reductions in spleen volume and symptom burden scores. These findings underscore the potential of Treg therapies in addressing diseases driven by dysregulated inflammation.
Insights into the Intestinal Microbiome
The Golden Globules in this category go to … Florent Malard, MD, PhD, Lawrence A. David PhD, and Tessa Andermann, MD, MPH, each of whom presented research during the Scientific Symposium, Interrogating the Impact of the Intestinal Microbiome on Transplant and Cellular Therapies, exploring the powerful connection between gut health and treatment outcomes. Whether it’s broad-spectrum antibiotics or allogeneic hematopoietic stem cell transplants, understanding how these treatments affect gut microbiota diversity could hold the key to reducing toxicities and improving efficacy. Understanding these interactions could lead to strategies that mitigate treatment-related toxicities and improve efficacy.
From time-tested treatments revitalized with modern approaches to optimizing solutions in gene therapy, the 2024 ASH Annual Meeting highlighted the incredible future and improved outcomes ahead for patients with classical hematology conditions.
