Tumor biomarkers for diagnosis, prognosis and targeted therapy | Signal Transduction and Targeted Therapy

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leukemia treatment :: Article Creator

Chromosomal Chaos Spurs Leukemia Treatment Breakthrough

German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

Chromosomal instability plays a crucial role in the progression of cancer: it shapes the properties of tumor cells and drives the development of therapy resistance. Scientists from the German Cancer Research Center (DKFZ), the Heidelberg Stem Cell Institute HI-STEM* and the European Molecular Biology Laboratory (EMBL) used state-of-the-art single-cell analysis methods to analyze the cellular heterogeneity of a specific form of acute myeloid leukemia. Their data show how genetic and non-genetic factors determine the functional heterogeneity of blood cancer cells and reveal new therapeutic targets.

In particular, under the selection pressure of cancer therapies, tumor cells undergo a veritable evolution to adapt to the changing conditions – and often escape the effects of therapy as a result. This evolution under therapeutic pressure is driven by a combination of genetic changes and non-genetic influences. Epigenetic modifications and changes in the transcriptome play a central role here, promoting the adaptation and activation of proliferation and survival programs.

/Public Release. This material from the originating organization/author(s) might be of the point-in-time nature, and edited for clarity, style and length. Mirage.News does not take institutional positions or sides, and all views, positions, and conclusions expressed herein are solely those of the author(s).View in full here.

First-in-Class Leukemia Treatment Approved By FDA

The FDA has approved a new drug called revumenib that can be taken orally to treat acute leukemia in patients 1 year or older. The drug will be marketed under the brand name Revuforj. 

Revuforj is a new class of drug for leukemia, meaning it works differently than other medicines that treat the disease. Unlike existing therapies, Revuforj directly targets the genetic changes that cause leukemia. It selectively blocks a protein (menin) that interacts with the KMT2A gene linked to leukemia, restoring normal function and halting the growth of leukemic cells.

Leukemia that is caused by this genetic change is fast-growing and associated with poor treatment outcomes, frequent relapses, and survival of less than a year. 

The new approval is a "major breakthrough," said Ghayas C. Issa, MD, associate professor of leukemia at The University of Texas MD Anderson Cancer Center, in a statement from Syndax, the drug's maker. 

"The significant clinical benefit and robust efficacy seen with Revuforj represents a substantial improvement over what has been historically observed in these patients with previously available therapies and has the potential to be an important new treatment option for patients," Issa said. 

The results of a 104-patient clinical trial assessing the drug's effectiveness and safety showed that 21% of patients achieved complete remission that lasted for about six and a half months. On average, it took about two months for remission to start. Twenty-four patients were able to proceed to stem cell transplants. 

The most common side effects include bleeding, infections, immune reactions, swelling, muscle pain, fatigue, appetite loss, nausea, constipation, diarrhea, electrolyte changes, blood abnormalities such as increased levels of liver enzymes, and a condition called QT prolongation where the heart takes longer than normal between beats. 

Syndax expects 110-milligram and 160-milligram tablets to be available at specialty distributors and pharmacies this month. Dosages of 25 milligrams intended for patients under 40 kilograms (about 88 pounds) are expected by early 2025. In the meantime, a liquid oral solution will be available to patients weighing less than 40 kilograms through an Expanded Access Program. You can talk to your health care provider for more details. 


Focusing Research On T-Cell ALL To Further Treatment Options

An expert highlighted unmet needs in treating T-cell acute lymphoblastic leukemia and where research may focus in the future.

Significant advancements in treating B-cell acute lymphoblastic leukemia (ALL) with innovative therapies like CAR-T cell therapy have surfaced in recent years. However, patients with T-cell ALL continue to face significant challenges, highlighting the need for more research, an expert said.

According to the National Cancer Institute, B-cell ALL is an aggressive type of leukemia when too many B-cell lymphoblasts, or immature white blood cells, are found in the blood and bone marrow. Of note, it is the most common type of ALL. In contrast, T-cell ALL is an aggressive leukemia type when too many T-cell lymphoblasts, or immature white blood cells, are found in blood and bone marrow.

Glossary

Bispecifics: a type of antibody that binds to two different antigens simultaneously.

CAR-T cell therapy: treatment when a patient's T cells, a type of immune system cell, are altered in a lab so they can attack cancer cells.

CD7-directed CAR-T cell therapy: T cells that are altered to specifically target the CD7 protein.

Tyrosine kinase inhibitor: a substance that blocks tyrosine kinases, which are a part of many cell functions including cell growth, signaling and division.

At the 42nd Annual Chemotherapy Foundation Symposium, CURE® spoke with Dr. Hannah Levavi to learn more about the unmet needs of patients with T-cell ALL experience and where the potential may lie for the treatment of the disease.

Levavi is an assistant professor of medicine, hematology and medical oncology at The Tisch Cancer Institute at Mount Sinai Hospital in New York.

Transcript:

In my mind, the biggest unmet need is in T-cell ALL. Unfortunately, things like bispecifics are much more complicated when you're trying to direct T cells toward other T cells, and the same exists with CAR-T [cell] therapy.

I don't go through CAR-T in any depth at all in my talk, just because of the scope of the talk, but CAR-T cells have really revolutionized the treatment of B-cell ALL. And we haven't achieved those same responses in T-cell ALL. And we don't really have great immunotherapy options in T-cell ALL.

So for patients who relapse with T-cell ALL, we're very limited. There are some CD7-directed CAR-T trials in T-cell ALL that I'm looking forward to hearing about. There are also some [Venclexta (venetoclax)] combinations that are agnostic to phenotypes, so they can be used in both B-cell ALL and T-cell ALL, and then some other creative combinations using things like TKIs (tyrosine kinase inhibitors) in T-cell ALL, which I'm hopeful will get more data and have some more options for those patients.

For more news on cancer updates, research and education, don't forget to subscribe to CURE®'s newsletters here.





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