The Best of ASH 2024

The Best of ASH is a selection of research abstracts that highlight the most cutting-edge science presented in the oral sessions during the annual American Society of Hematology (ASH) meeting.

This year’s session was presented by the 2024 Scientific Program Co-Chairs Drs. Jennifer Trowbridge and Sant-Rayn Pasricha.

In this article, we'll cover the most relevant abstracts for researchers and healthcare professionals working in hematology and blood cancers. The board considered the following themes as most influential for selecting the abstracts: 

• New mechanisms of cancer cell selection and dominance in cancer blood cell formation
• Emerging treatment strategies in acute myeloid leukemia (AML)
• Prevention and intervention therapies in multiple myeloma and myeloproliferative neoplasms (MPN)
• Considerations for standard-of-care in lymphocytic leukemia and lymphoma

The Best of ASH for Blood Cancers  

1. Targeted protein degradation reveals a repressive role of MECOM at the CEBPA Locus to prevent differentiation in high-risk acute myeloid leukemia (AML) 

This research delves into the role of the MECOM gene in AML. It reveals that MECOM acts as a key regulator of gene expression, specifically repressing genes that promote cell differentiation. It also may influence the lack of transformation of new blood cells, making them blasts (which are the main identifier of AML cells). 

What are the therapeutic implications of this study?

• Targeting MECOM could be a new and effective way of treating AML. 

To explore this abstract, click here. 

2. Development of a first-in-class CAR-T therapy against carleticulin-mutant neoplasms and evaluation in the relevant human tissue environment

This research focuses on a treatment called CAR-T cell therapy. This new CAR-T targets a specific mutation in the CALR gene found in certain types of myeloproliferative neoplasms (MPNs), such as myelofibrosis.

It is pre-clinical, so patients haven't received it yet, but in experimental models, this therapy has been effective. Researchers also explored combining this CAR-T cell therapy with other treatments, such as bispecific antibody therapies that are limited in patients where other treatments, like JAK inhibitors, are insufficient.

To explore this abstract, click here. 

3. Phase 3 randomized study of daratumumab monotherapy versus active monitoring in patients with high-risk smoldering multiple myeloma: primary results of the AQUILA study

Smoldering myeloma is a precursor to multiple myeloma, with limited treatment options currently available for high-risk patients. The AQUILA study explores a new treatment using daratumumab, a therapy already proven effective in active myeloma. Based on these findings, the company has submitted an application to the FDA for daratumumab's approval to treat high-risk smoldering myeloma.

We cover more details in the following articles: 

• Landmark Study Shows Daratumumab Significantly Delays Progression in Smoldering Myeloma
• New Treatment Coming for High-Risk Smoldering Myeloma?

4. Fixed-duration acalabrutinib + venetoclax with or without obinutuzumab vs chemoimmunotherapy for first-line treatment of chronic lymphocytic leukemia (CLL): interim analysis of the multicenter, open-label, randomized, phase 3 AMPLIFY trial 

CLL therapies usually contain BTK inhibitors, venetoclax, and/or immunotherapy. This research aims to assess the safety and efficacy of these combinations and proves a low incidence of heart-related side effects typically associated with BTK inhibitors. 

We cover more comprehensive details from the session given by the lead investigator here.

5. Ibrutinib-rituximab is superior to rituximab chemotherapy in previously untreated older mantle cell lymphoma patients: results from the international randomized controlled trial, ENRICH

This new combination is used to treat mantle cell lymphoma, a type of B-cell non-Hodgkin lymphoma, in which aggressive treatment options are not considered appropriate for older patients. Considering that the median diagnosis age is 71 years old, there is a need for endurable treatment options. The current standard of care includes immunotherapy, R-CHOP, and bendamustine. 

This phase 2/3 trial provides strong evidence that ibrutinib-rituximab should be considered a standard of care for first-line treatment of older patients with mantle cell lymphoma. The median progression-free survival (PFS) for patients who took ibrutinib-rituximab was 65.3 months compared to 43.4 months in the R-CHOP arm. 

This finding has the potential to significantly improve outcomes for elderly patients with mantle cell lymphoma. 

To explore this abstract, click here. 

6. Real-world outcomes of CD19 CAR-T cell therapy in adult patients with relapsed and refractory transformed indolent lymphoma 

Indolent lymphoma is associated with lower overall survival; that's why understanding real-world outcomes of an effective therapy such as CAR-T is important, as there is not yet a standard of care approach for this group of patients. This study demonstrated that patients with transformed indolent lymphoma had high complete remission (CR) rates in response to CD19 CAR-T therapy, slower onset of cytokine release syndrome CRS (common in CAR-T), and lower incidence of ICANS. 

The conclusion is that the results of this study suggest that CD19 CAR-T is highly effective for treating transformed indolent lymphoma.

To check out this abstract, click here. 

7. In Vivo barcoded CRISPR-Cas9 screen identifies Ncoa4-mediated ferritinophagy as a dependence in Tet2-deficient hemopoiesis

This abstract explores the role of the TET2 gene in clonal hematopoiesis (CH), a condition characterized by the expansion of mutated blood stem cells. To identify the genes involved, the researchers conducted an in vivo CRISPR-Cas9 screen, which revealed NCOA4, a regulator of iron metabolism. Cells with mutations in the gene TET2  exhibit increased mitochondrial activity, which demands significant iron for optimal function.

What are the therapeutic implications of this study?

• Understanding the role of iron metabolism can lead to therapies that target it. NCOA4 could mitigate the growth advantage of TET2-mutant cells, offering a new path for therapeutic intervention in clonal hematopoiesis and related blood disorders.

To read more on this abstract, click here. 

8. DnmT3a controls hematopoietic stem cells via DNA methylation-independent regulation of telomeres

Understanding the functions of DNMT3A may provide insights into the development of blood disorders associated with DNMT3A mutations. This study suggests that DNMT3A has functions beyond DNA methylation, including a potential role in regulating telomere length and DNA damage response. This role is also essential for cell longevity and function.

Read more about this abstract by clicking here. 

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