The Best of ASH is a selection of abstracts that highlights the most cutting-edge science presented in the oral sessions during the annual 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 abstracts they selected that are most relevant 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
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 or its downstream targets could potentially induce the differentiation of AML cells, offering a new therapeutic approach.
This research focuses on CAR-T cell therapy to target a specific mutation in the CALR gene found in certain types of myeloproliferative neoplasms (MPNs). It is pre-clinical, so patients haven't received it yet, but in experimental models, this therapy has shown efficacy. Researchers also explored the potential of combining this CAR-T cell therapy with other treatments, such as antibody/BiTE therapies that are limited in patients where JAK inhibitors are insufficient.
3. Phase 3 randomized study of daratumumab monotherapy vs active monitoring in patients with high-risk smoldering multiple myeloma: primary results of the AQUILA study
This is a major event for smoldering myeloma as it could signify the first approved treatment for smoldering myeloma, of which the current standard of care is observation. We cover more details in the following articles:
The results discussed in the session address the benefit of daratumumab continued beyond the 3 years of treatment, with significant differences observed at 60 months after randomization. There was a low rate of discontinuation, and no serious side effects were reported.
CLL therapies usually contain BTK inhibitors, venetoclax, and/or immunotherapy. This research aims to assess the safety and efficacy of these combinations, and they also prove a low incidence of heart-related side effects that are typically associated with BTK inhibitors. We cover more comprehensive details from the session given by the lead investigator here.
In this type of B-cell non-Hodgkin lymphoma, 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 standard of care includes immunotherapy, R-CHOP, and bendamustine.
This phase II/III 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 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 improve outcomes for this patient population significantly.
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. Front-line therapies in lymphocytic leukemias and lymphomas have reduced the need for chemotherapy, thereby reducing the risk of side effects.
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 potentially mitigate the growth advantage of TET2-mutant cells, offering a new path for therapeutic intervention in clonal hematopoiesis and related blood disorders.
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.
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The Best of ASH is a selection of abstracts that highlights the most cutting-edge science presented in the oral sessions during the annual 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 abstracts they selected that are most relevant 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
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 or its downstream targets could potentially induce the differentiation of AML cells, offering a new therapeutic approach.
This research focuses on CAR-T cell therapy to target a specific mutation in the CALR gene found in certain types of myeloproliferative neoplasms (MPNs). It is pre-clinical, so patients haven't received it yet, but in experimental models, this therapy has shown efficacy. Researchers also explored the potential of combining this CAR-T cell therapy with other treatments, such as antibody/BiTE therapies that are limited in patients where JAK inhibitors are insufficient.
3. Phase 3 randomized study of daratumumab monotherapy vs active monitoring in patients with high-risk smoldering multiple myeloma: primary results of the AQUILA study
This is a major event for smoldering myeloma as it could signify the first approved treatment for smoldering myeloma, of which the current standard of care is observation. We cover more details in the following articles:
The results discussed in the session address the benefit of daratumumab continued beyond the 3 years of treatment, with significant differences observed at 60 months after randomization. There was a low rate of discontinuation, and no serious side effects were reported.
CLL therapies usually contain BTK inhibitors, venetoclax, and/or immunotherapy. This research aims to assess the safety and efficacy of these combinations, and they also prove a low incidence of heart-related side effects that are typically associated with BTK inhibitors. We cover more comprehensive details from the session given by the lead investigator here.
In this type of B-cell non-Hodgkin lymphoma, 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 standard of care includes immunotherapy, R-CHOP, and bendamustine.
This phase II/III 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 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 improve outcomes for this patient population significantly.
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. Front-line therapies in lymphocytic leukemias and lymphomas have reduced the need for chemotherapy, thereby reducing the risk of side effects.
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 potentially mitigate the growth advantage of TET2-mutant cells, offering a new path for therapeutic intervention in clonal hematopoiesis and related blood disorders.
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.
With Healthtree, You Can Contribute to Research Too!
Join HealthTree, the platform that powers life-saving research!
CREATE MY FREE ACCOUNT
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