Bengaluru: Two groups of US researchers have reported promising results from a Phase 1 trial of a drug for advanced and treatment-resistant leukemia in separate papers.
The new drug, known as revumanib, was tested on 60 patients with an acute form of the disease, and more than half experienced complete or partial remission. MMore than three-quarters of the ore of the latter group was still in recovery two months after discounting.
Findings from this Phase 1 trial , Held at nine sites in the US between 2019 and 2022 with a limited number of volunteers , show early evidence of a potential treatment for acute leukemia.
they were published in the magazine Nature Wednesday as part of a study conducted by Ghayas Issa University of Texas at Houston MD Anderson Cancer Centerand their allies.
Also in a related Phase 1 study published In Nature On the same day, researchers including Scott Armstrong Dana-Farber Cancer Institute in Bostoninvestigated specific mutations in the identified genes that may result in resistance to rivumanib.
Understanding these “treatment-escape” routes would provide valuable information for tackling drug-resistant therapies, such as those for leukemia.
Leukemia is a cancer of the blood, originating in the bone marrow, where red blood cells are produced. There are acute and chronic leukemia types, and all types are combined. accounted for About 4 percent of global cancer deaths in 2020.
Good night Acute and drug-resistant leukemia is significantly worse, sometimes as low as 8 percent.
Read also: 1 in 5 cervical cancer cases in India, almost 1 in 4 deaths, finds Lancet study
Menin, and the role of rivumanib as a menin inhibitor
genes in human body responsible for Acute leukemia has been well studied and established. these genes to go past set of specific mutations as the disease developsWhich is also documented.
Acute leukemia is typically characterized by either a mutation on the NPM1 gene or a rearrangement of the KMT2Ar gene. Both of these genes have been shown to play a role in the progression of the disease.
There are no current treatments that target these genes. preliminary, pre-clinical studies have shown that menin, a protein responsible for suppressing tumors, enabled the progression of mutations in two leukemia genes.
This indicates that menin plays an important role in cancer facilitation, suggesting that menin inhibition may reverse or halt cancer progression.
Revumanib, which has both efficacy and safety phase 1 Studies are testing it is believed to be a potent, oral, selective inhibitor of menin.
remission with revumanib
According to the first study by Issa and colleagues, 68 patients were treated with an experimental dose of revumanib, formerly known as SNDX-5613. These included 60 adults and 8 people under the age of 18. , The first person to be treated with this medicine.
60 out of 68 are eligible for evaluation. At least 53 percent of these 60 participants experienced some degree of remission, with 30 percent (18 of 60) having stopped cancer growth. To experience complete relaxation.
Of these 18, 78 percent had no measurable residual disease after only two months.
“We found an encouraging clinical benefit with deep molecular remission and minimal toxicity in a large population of both children and adults with advanced acute leukemia,” the paper’s authors wrote.
While the results are promising, they are not without side-effects. More than three-quarters of participants experienced at least one adverse event such as irregular heartbeat, nausea or vomiting.
But his recovery provides a strong basis for future Phase 1 studies that include more people, use a different formula for the drug, and test for efficacy.
combating drug resistance
In a second analysis of the data, Armstrong and colleagues studied some of the mutations in genes that exhibit selective resistance to menin inhibition and drugs such as revumanib.
They identified mutations in the MEN1 gene, which encodes menin. These mutations were found in many patients who initially responded to the drug, but stopped after some time.
The researchers found that the mutations can result in resistance to menin inhibition through changes at the drug-binding site, resulting in individuals becoming treatment-resistant.
“To our knowledge, this study is the first to demonstrate that a chromatin-targeted therapeutic drug exerts sufficient selection pressure in patients to drive the evolution of escape mutants that lead to sustained chromatin occupancy, a mechanism of therapeutic resistance.” suggests a general mechanism,” wrote the authors.
Identifying pathways that lead to drug resistance is important not only to understand the different ways to combat drug resistance for treatment-resistant diseases, but also to improve the formulations of existing drugs for better efficacy.
(Edited by Gitanjali Das)
Read also: Gender skew in cancer diagnosis? Only 1 out of 3 boys in Delhi and 2 out of 5 girls in Chennai