PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Targeting menin induces responses in acute leukemias with KMT2A rearrangements or NPM1 mutations

2023-03-15
(Press-News.org) Researchers from The University of Texas MD Anderson Cancer Center showed that inhibiting menin with revumenib, previously known as SNDX-5613, yielded encouraging responses for advanced acute leukemias with KMT2A rearrangements or mutant NPM1. Findings from the Phase I AUGMENT-101 trial were published today in Nature.

The overall response rate among 60 patients was 53%, and the rate of complete remission or complete remission with partial hematologic recovery was 30%, with 78% of patients achieving clearance of measurable residual disease. Responses were seen across multiple dose levels. The results originally were presented at the 2022 American Society of Hematology (ASH) Annual Meeting.

“Acute leukemias with KMT2A rearrangements are difficult to treat and NPM1 mutations are the most common genetic alteration in acute myeloid leukemia. These subsets have no specifically approved targeted therapies.,” said study lead Ghayas Issa, M.D., assistant professor of Leukemia. “I am encouraged by these results, which suggest that revumenib may be an effective oral targeted therapy for patients with an acute leukemia caused by these genetic alterations. These response rates, especially rates of residual disease clearance, are the highest we have seen with any monotherapy used for these resistant leukemia subsets.”

In KMT2A-rearranged or NPM1-mutant acute leukemias, the interaction of the menin protein with KMT2A (also known as MLL) is critical in driving expression of leukemia-promoting genes. Leukemias with KMT2A rearrangements occur in infants, children and adults, and NPM1 mutations are the most common genetic alteration in acute myeloid leukemia. Preclinical studies suggested that targeting the interaction between menin and KMT2A may be an effective strategy for treating cancers with these mutations.

This is the first evidence showing the safety and clinical activity of menin inhibition in acute leukemia, and the data demonstrate the potential for targeting scaffold proteins that are shown to be vulnerable points in specific cancers. According to Issa, targeting menin disrupts the gene transcription machinery and shifts gene expression in cancer cells from a leukemia pattern to a normal pattern, ultimately leading to remission.

The AUGMENT-101 study is a first-in-human, open-label, dose-escalation and dose-expansion study to evaluate the safety and anti-tumor activity of revumenib — an oral small-molecule inhibitor of the menin-KMT2A interaction — in children and adults with advanced KMT2A-rearranged or NPM1-mutant acute myeloid or lymphoid leukemias.

The trial enrolled 68 patients with a median age of 43, including children as young as 10 months of age. Disease types included acute myeloid leukemia (82%), acute lymphocytic leukemia (16%) and mixed phenotype acute leukemia (2%). Among enrolled patients, 67.6% had KMT2A rearrangements, 20.6% had NPM1 mutations and 11.8% had other genotypes. Patients were heavily pretreated with a median of four prior lines of therapy and 46% had a prior allogeneic stem cell transplant. 

The median duration of response was 9.1 months and median overall survival was seven months. Twelve patients proceeded to allogeneic stem cell transplant following response to revumenib.

There were no treatment discontinuations due to treatment-related adverse events.

Differentiation syndrome — an occurrence previously described with other targeted therapies in myeloid leukemias leading to differentiation of leukemia cells into normal hematopoietic cells — was reported in 11 patients. Manifestations of differentiation syndrome in all patients resolved with steroids and/or hydroxyurea, and all were grade 2 or below.

The most common treatment-related adverse event was asymptomatic prolongation of the QT interval on electrocardiography, with a grade 3 rate of 13%. Other grade three or above treatment-related adverse events included diarrhea (3%), fatigue (3%), anemia (3%), tumor lysis syndrome (2%), neutropenia (2%), thrombocytopenia (2%), hypercalcemia (2%) and hypokalemia (2%).

“The responses in this trial show that menin inhibitors may be a promising treatment option that is well tolerated by patients and could be the newest addition to successful targeted therapies for acute leukemia,” Issa said. “I look forward to additional data from this and future trials to inform the potential opportunity to offer this targeted treatment to more patients.”

Enrollment for the phase II cohort of the trial is ongoing. Future trials of revumenib will test combinations with other agents in various settings, including newly diagnosed leukemias, relapsed or refractory disease, and maintenance therapy, for KMT2A-rearranged or NPM1-mutant leukemias and other leukemias susceptible to menin inhibition.

This study was supported by Syndax Pharmaceuticals. Issa serves as a consultant to Syndax Pharmaceuticals. A full list of co-authors and disclosures is available here.

END


ELSE PRESS RELEASES FROM THIS DATE:

Bird flu associated with hundreds of seal deaths in New England in 2022, Tufts researchers find

2023-03-15
Researchers at Cummings School of Veterinary Medicine at Tufts University found that an outbreak of highly pathogenic avian influenza (HPAI) was associated with the deaths of more than 330 New England harbor and gray seals along the North Atlantic coast in June and July 2022, and the outbreak was connected to a wave of avian influenza in birds in the region. The study was published on March 15 in the journal Emerging Infectious Disease. HPAI is more commonly known as bird flu, and the H5N1 strain has been responsible for about 60 million poultry ...

Designing more useful bacteria

Designing more useful bacteria
2023-03-15
In a step forward for genetic engineering and synthetic biology, researchers have modified a strain of Escherichia coli bacteria to be immune to natural viral infections while also minimizing the potential for the bacteria or their modified genes to escape into the wild. The work promises to reduce the threats of viral contamination when harnessing bacteria to produce medicines such as insulin as well as other useful substances, such as biofuels. Currently, viruses that infect vats of bacteria can halt production, compromise ...

New laser technology developed by EPFL and IBM

New laser technology developed by EPFL and IBM
2023-03-15
Scientists at EPFL and IBM have developed a new type of laser that could have a significant impact on optical ranging technology. The laser is based on a material called lithium niobate, often used in the field of optical modulators, which controls the frequency or intensity of light that is transmitted through a device. Lithium niobate is particularly useful because it can handle a lot of optical power and has a high “Pockels coefficient”, which means that it can change its optical properties when an electric field is applied to it. The researchers achieved their breakthrough by combining ...

How genome doubling helps cancer develop

How genome doubling helps cancer develop
2023-03-15
A single cell contains 2-3 meters of DNA, meaning that the only way to store it is to package it into tight coils. The solution is chromatin: a complex of DNA wrapped around proteins called histones. In the 3D space, this complex is progressively folded into a multi-layered organization composed of loops, domains, and compartments, which makes up what we know as chromosomes. The organization of chromatin is closely linked to gene expression and the cell’s proper function, so any problems in chromatin structure can have detrimental effects, including the development of cancer. A common event in around 30% of all human cancers is “whole genome doubling” ...

Magnificent wiring

Magnificent wiring
2023-03-15
NEW YORK – For a functioning brain to develop from its embryonic beginnings, so much has to happen and go exactly right with exquisite precision, according to a just-so sequence in space and time. It’s like starting with a brick that somehow replicates and differentiates into a hundred types of building materials that also replicate, while simultaneously self-assembling into a handsome skyscraper replete with functioning thermal, plumbing, security and electrical systems. The accompanying microscope image, from ...

Self-driven laboratory, AlphaFlow, speeds chemical discovery

2023-03-15
A team of chemical engineering researchers has developed a self-driven lab that is capable of identifying and optimizing new complex multistep reaction routes for the synthesis of advanced functional materials and molecules. In a proof-of-concept demonstration, the system found a more efficient way to produce high-quality semiconductor nanocrystals that are used in optical and photonic devices. “Progress in materials and molecular discovery is slow, because conventional techniques for discovering new chemistries rely on varying ...

Minimizing electric vehicles’ impact on the grid

2023-03-15
National and global plans to combat climate change include increasing the electrification of vehicles and the percentage of electricity generated from renewable sources. But some projections show that these trends might require costly new power plants to meet peak loads in the evening when cars are plugged in after the workday. What’s more, overproduction of power from solar farms during the daytime can waste valuable electricity-generation capacity. In a new study, MIT researchers have found that it’s possible to mitigate or eliminate both these problems without the need for ...

Estimated COVID-19 mRNA vaccine effectiveness, illness severity during Omicron BA.4 and BA.5 periods

2023-03-15
About The Study: In this case-control study of COVID-19 vaccines and illness, vaccine effectiveness associated with protection against medically attended COVID-19 illness was lower with increasing time since last dose; estimated vaccine effectiveness was higher after receipt of one or two booster doses compared with a primary series alone.  Authors: Ruth Link-Gelles, Ph.D., M.P.H., of the Centers for Disease Control and Prevention COVID-19 Response Team in Atlanta, is the corresponding ...

Effect of sleep changes on health-related quality of life in healthy children

2023-03-15
About The Study: Results of this secondary analysis of a randomized trial involving 100 healthy children ages 8 to 12 indicated that even 39 minutes less of sleep per night for one week significantly reduced several facets of health-related quality of life in children. This finding shows that ensuring children receive sufficient good-quality sleep is an important child health issue.  Authors: Rachael W. Taylor, Ph.D., of the University of Otago in Dunedin, New Zealand, is the corresponding ...

New definitions of multimorbidity may improve clinical decision-making for older surgical patients

New definitions of multimorbidity may improve clinical decision-making for older surgical patients
2023-03-15
Key Takeaways New definitions surpass conventional definitions: The new study developed and validated better surgical, specialty-specific, multimorbidity definitions based on distinct characteristics of older inpatient general, orthopedic, and vascular surgery patients. Mortality risk is higher for some patients: For some types of surgery, patients with certain combinations of comorbidities face significantly higher 30-day mortality risk than patients who are lower risk. Helping assess overall risk: Researchers anticipate that the new multimorbidity definitions will help surgeons better explain the risks associated with any given procedure to ...

LAST 30 PRESS RELEASES:

The research was wrong: study shows moderate drinking won’t lengthen your life

Save your data on printable magnetic devices? New laser technique’s twist might make this reality

Early onset dementia more common than previously reported – the incidence of Alzheimer’s disease seems to be on the rise

Pesticides potentially as bad as smoking for increased risk in certain cancers

NUS researchers develop new battery-free technology to power electronic devices using ambient radiofrequency signals

New protein discovery may influence future cancer treatment

Timing matters: Scripps Research study shows ways to improve health alerts

New gene therapy approach shows promise for Duchenne muscular dystrophy

Chemical analyses find hidden elements from renaissance astronomer Tycho Brahe’s alchemy laboratory

Pacific Northwest launches clean hydrogen energy hub

Tiny deletion in heart muscle protein briefly affects embryonic ventricles but has long-term effects on adult atrial fibrillation

Harms of prescribing NSAIDs to high risk groups estimated to cost NHS £31m over 10 years

Wearing a face mask in public spaces cuts risk of common respiratory symptoms, suggests Norway study

Some private biobanks overinflating the value of umbilical cord blood banking in marketing to expectant parents

New research in fatty liver disease aims to help with early intervention

Genetics reveal ancient trade routes and path to domestication of the Four Corners potato

SNIS 2024: New study shows critical improvements in treating rare eye cancer in children

Wearable devices can increase health anxiety. Could they adversely affect health?

Addressing wounds of war

Rice researchers develop innovative battery recycling method

It’s got praying mantis eyes

Stroke recovery: It’s in the genes

Foam fluidics showcase Rice lab’s creative approach to circuit design

Montana State scientists publish evidence for new groups of methane-producing organisms

Daily rhythms depend on receptor density in biological clock

New England Journal of Medicine publishes outcomes from practice-changing E1910 trial for patients with BCR::ABL1-negative B-cell precursor acute lymphoblastic leukemia

Older adults want to cut back on medication, but study shows need for caution

Nationwide flood models poorly capture risks to households and properties

Does your body composition affect your risk of dementia or Parkinson’s?

Researchers discover faster, more energy-efficient way to manufacture an industrially important chemical

[Press-News.org] Targeting menin induces responses in acute leukemias with KMT2A rearrangements or NPM1 mutations