Innovation in hematology often brings to mind new drugs with novel mechanisms of action — and rightly so. However, innovation extends beyond the introduction of groundbreaking therapies. Expanding the indications of established treatments, challenging conventional paradigms in disease biology, and reimagining how health care is delivered are equally vital pathways for progress. After all, optimizing existing resources and improving access are just as crucial for advancing the field as the development of new technologies.
Old Drugs, New Uses
Mass production of synthetic erythropoietin (EPO) in the 1980s changed the natural history of chronic kidney disease and transformed the treatment landscape. Could patients with sickle cell disease (SCD) derive as much benefit? The ACHiEvE-SCD study explores the use of escalated doses of epoetin alfa in patients with SCD on stable-dose hydroxyurea and demonstrates, with limited drug-related side effects, that EPO increases hemoglobin independent of patient’s baseline kidney function. “We are excited about the potential and immediate impacts of this pilot study, as it optimizes the use of existing drugs that are available in most countries and provides initial guidance on the dosing of EPO in SCD,” said Julia Z. Xu, MD, MScGH, who will be presenting the results of this study today (2:45 p.m. - 3:00 p.m., CC, Hall B).
Often, the most impactful outcomes come from rethinking how health care is delivered. Intranasal fentanyl may redefine the concept of "the right drug at the right time" for managing acute pain in patients with SCD who present to the emergency department, potentially reducing hospital admissions.
“Improving the care we deliver for individuals living with sickle cell disease is work that cannot be done in isolation,” said Seethal A. Jacob, MD, MS, senior author of a study showcasing the power of coordination and teamwork to improve patient outcomes, the results of which will be presented later today (4:45 p.m. - 5:00 p.m., CC, Room 30). “By utilizing a multidisciplinary team — led by Dr. Olufunke Martin — to develop, champion, and implement our emergency department pain management pathway, we were not only able to improve acute care delivery for our patient but also develop a health system-wide quality metric for sickle cell pain management.”
New Drugs, New Solutions (and Problems)
There is still plenty of excitement on the “new agent” front. The novel oral therapy, ILX-002 is a first-in-class oral and once-daily drug, that directly inhibits hemoglobin S polymerization by mimicking a rare protective hemoglobin variant, adding to the repertoire of disease-modifying drugs in SCD. In preclinical models, ILX-002 normalized hemoglobin levels, reduced reticulocyte counts, and decreased spleen size in mice. “The significant hematologic improvements seen in humanized mice treated with ILX-002 highlight its promise as a simple, daily oral treatment for sickle cell disease,” said Osheiza Abdulmalik, DMV, who will be presenting his team’s study abstract this afternoon (3:00 p.m. – 3:15 p.m., CC, Room 31).
A broad repertoire of alternatives to standard half-life factor replacements, including extended half-life products, bispecific antibodies, and rebalancing agents, is now readily available for clinical use in patients with severe inherited bleeding disorders. With robust data to back up their safety, the “real-world” use challenges, such as treatment of breakthrough bleeding events and drug-related adverse events, emerge. Steven W. Pipe, MD, will present data on management of breakthrough bleeding in patients on the small interfering RNA-based rebalancing therapy fitusiran (12:15 p.m. - 12:30 p.m., CC, Room 29). According to Dr. Pipe, prophylaxis with fitusiran “modulates thrombin generation by reducing antithrombin levels, providing effective bleed protection as well as allowing for markedly reduced doses of factor products needed to treat breakthrough bleeding events.”
Risk of thrombosis is also clinically impactful with the newer hemostatic agents. Data from the phase III Explorer 7 study on concizumab, an anti-tissue factor pathway inhibitor, will be presented on Monday (10:30 a.m. - 10:45 a.m., CC, Room 30). The high efficacy and lack of safety concerns in terms of thrombotic events should provide reassurance following the safety signals in the earlier stage trials. Along with the newly U.S. Food and Drug Administration-approved marstacimab, these drugs are a big step for patients with hemophilia B with inhibitors or those with other rare inherited disorders or bleeding of unknown cause.
New Clinical Entities
At #ASH24, innovation does not stop with drugs. Previously unrecognized biological entities, such as clonal hematopoiesis of indeterminate potential, have emerged as risk factors for common complications, like cancer-associated venous thromboembolism (VTE).
“Clonal hematopoiesis has been associated with decreased survival and risk of therapy-related myeloid neoplasms in lymphoma patients treated with autologous transplantation, and we now show an increased risk of [VTE], particularly in patients harboring mutations in PPM1D and TP53,” explained Radhika Gangaraju, MD, MSPH, who will present her research team’s study abstract this morning (9:45 a.m. – 10:00 a.m., CC, Room 24). “Testing for clonal hematopoiesis at the time of autologous transplant may help in identifying high-risk populations for targeted interventions.” Dr. Gangaraju will also serve as moderator of a morning session during which her work will be highlighted. This must-attend session will showcase a broad spectrum of highly selected clinical cohorts and population studies exploring the effect of non-driver genetic variants and germline genetic modifiers in the determination of VTE and cardiovascular risk (9:30 a.m. - 11:00 a.m.)
Get ready to be blown away by the blend of old and new in classical hematology and experience how making the most of the staples can be as exciting as experimenting with new ingredients!
