Emerging Trends in Hematology – ASH 2023 Highlights

Medical Hematology Experts Share Highlights from the 65th ASH Conference

In December 2023, Medpace classic and malignant hematology experts attended the 65^th American Hematology Society (ASH) conference in San Diego, CA. Learn more from Blythe Thomson, MD, Senior Vice President, Medical Department, Hematology and Oncology, as she recaps highlights from the conference.  

Emerging Trends in Hematology and Oncology

Classic hematology has displayed significant promise in the clinical space following the approvals of CASGEVY^®1 and LYFGENIA^®2. The presentation by H. Frangoul and colleagues of the Exa-cel Phase 3 clinical trial demonstrated the utility of editing ex-vivo with CRISPR-Cas9 technology of the erythroid-specific enhancer region of BCL11A³. This increased hemoglobin F production resulted in 96.7% of subjects with severe Sickle Cell Disease being free of vaso-occlusive events and 100% of subjects being freed from hospitalization. The recent approved therapies not only underscore the potential for treating Sickle Cell Disease (SCD), but also demonstrate a bright future for hematological advancements. Comparable data was additionally presented by F. Locatelli in patients with severe beta thalassemia who received Exagamglogene autotemcel with >90% of patients achieving transfusion independence with improved quality of life.⁴

Another potentially practice-changing therapy was presented for patients with severe hemophilia A and moderate to severe hemophilia B. Marstacimab, a novel monoclonal antibody that neutralized tissue factor pathway inhibitor, thus increasing thrombin through the extrinsic coagulation pathway was investigated was presented.⁵  Subjects with either Hemophilia A or Hemophilia B without inhibitors were enrolled in the single arm study presented. The annual bleeding rate dramatically decreased in both the on-demand group and the routine prophylaxis group. This approach offers a new approach to management of patients with Hemophilia. However, within promise lies challenges, requiring a concerted effort to ensure these complex therapies remain at the forefront of medical advancement and the global access to these therapies remains a challenge.   

For patients undergoing hematopoietic cell transplantation, the plenary session provided an update on potential treatment for chronic graft versus host disease (GVHD). Over 75% of subjects who had failed prior FDA approved therapy demonstrated response in the randomized Phase 2 study of Axatilimab  with a median failure free survival of 17 months, offering new hope to patients with debilitating chronic GVHD.⁶ Finally, the role of the microbiome in graft versus host disease (GVHD) is a new avenue of clinical and translational research in patients post transplant with new explorations of the role of the microbiota composition in the alloreactive T cell response in GVHD.⁷

Malignant hematology demonstrated the continued importance of minimal residual disease (MRD) in multiple myeloma, Hodgkin disease and acute leukemias with introduction of new agents to standard regimens improving the potential of additional patients achieving MRD negative status.^8,9,10

ASH 2023 incorporated a variety of topics, including therapeutic and practice methodologies to address existing hurdles while keeping pace with the evolving landscape of hematologic developments. Other topics highlighted novel avenues, such as increased focus on new therapies such as immunotherapy, cell and gene therapies, and rare diseases, in addition to technological advancements that are defining the forefront of hematology.  Perhaps the most important take home message for all attendees at ASH was the criticality of increasing access to clinical trials and novel therapies to a more diverse population.   

An Industry Leader in Hematology Clinical Research

As we reflect on ASH 2023, a pivotal theme emerges—the imperative for collaboration is paramount in comprehending the multifaceted world of hematology clinical research. Understanding the biology of hematological malignancies, comprehending the evolving treatment landscape by following current guidelines and clinical practices, and capitalizing on the latest technological advancements is critical to your trial’s success. From inception to post-approval, navigating this complex terrain mandates a strategic approach that overcomes the challenges posed, such as trial site competition or difficult-to-recruit populations.  

In this dynamic landscape, Medpace is a trusted ally, offering not just expertise, but a comprehensive understanding of the hematological clinical development process. Exceed the ongoing demands, ensure a competitive advantage, and be confident in the successful design and conduct of your hematology or oncology study with guidance from the experienced team of specialized oncology & hematology experts at Medpace. We have conducted over 300 Phase I-IV hematology and oncology trials, in over 45 countries, including the US, Europe, and Asia Pacific. Our deep and broad experience includes having conducted research in a full range of solid tumor and hematologic indications and therapies from classic multi-cytotoxic agents to cutting-edge and targeted therapies.  

We welcome the opportunity to talk about your upcoming clinical development in hematology and oncology. Learn more about our capabilities in hematology and oncology and contact us to connect with our internal experts. 

List of References

1. CASGEVY. Food and Drug Administration Website. https://www.fda.gov/vaccines-blood-biologics/casgevy. Accessed December 14, 2023.  ↩︎
2. LYFGENIA. Food and Drug Administration Website. https://www.fda.gov/vaccines-blood-biologics/lyfgenia. Accessed December 14, 2023.  ↩︎
3. Frangoul, H et al. Exagamglogene Autotemcel for severe Sickle Cell Disease. Proc American Society of Hematology, 2023.  ↩︎
4. Locatelli, F et al. Exagamglogene Autotemcel for Transfusion Dependent B-Thalessemia, Proc American Society of Hematology, 2023.  ↩︎
5. Matino D et al. Efficacy and Safety of the Anti-Tissue Factor Pathway Inhibitor Marstacimab in Participants with Severe Hemophilia without inhibitors: Results of the Phase 3 Basis Trial. Proc American Society of Hematology, 2023.  ↩︎
6. Wolff D et al. Safety and Efficacy of Axatilimab at 3 Different Doses in Patients with Chronic Graft-Versus Host Disae (AGAVE-201). Proc American Society of Hematology, 2023.  ↩︎
7. Yeh AC et al. Microbiotica-Specific T Cells Contribute to Graft-Versus Host Disease after Allogeneic Stem Cell Transplantation. Proc American Society of Hematology, 2023.  ↩︎
8. Gay F et al. Results of the Phase III Randomized Iskia Trial: Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone vs Carfilzomib-Lenalidomide-Dexamethasone as Pre-Transplant and Post-Transplant Consolidation in Newly Diagnosed Multiple Myeloma Patients. Proc American Society of Hematology, 2023.  ↩︎
9. Hillmen P et al. Ibrutinib Plus Venetoclax with MRD-Directed Duration of Treatment is Superior to FCR and is a New Standard of Care for Previously Untreated CLL: Report of the Phase III UK NCRI FLAIR Study. Proc American Society of Hematology, 2023.  ↩︎
10. Othman J et al. The Benefit of Allogeneic Transplant in 1^st Complete Remission in NPM1 Mutated AML with or without FLT3 ITD is Restricted to Those Testing MRD Positive after Induction – An Analysis of the UK NCRIAML17 and AML 19 Studies. Proc American Society of Hematology, 2023.  ↩︎