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Scientists are testing new drugs to treat different types of leukemia. Luis Velasco/Stocksy
  • More than 474,000 people globally have leukemia, and acute leukemia is the most aggressive type.
  • In a new clinical trial, of the 60 people with certain types of acute leukemia who took a new drug called revumenib, 30% experienced complete remission of the disease.
  • Researchers are now hoping to carry out phase 2 trials and further studies to confirm these benefits.

As of 2020, more than 474,000 people around the world have leukemia — a cancer of the blood.

Of the two main types of leukemia, acute leukemia is the most aggressive causing cells to multiply very rapidly in the blood and blood marrow. Although there are treatments for acute leukemia, survival rates depend on a variety of factors including a person’s age and how progressive their disease is.

To add to treatments available for acute leukemia, Syndax Pharmaceuticals, Inc. recently announced Phase 1 results for its Phase 1/2 AUGMENT-101 trial of revumenib in people with nucleophosmin mutant (mNPM1) and KMT2A-rearranged (KMT2Ar) relapsed/refractory (R/R) acute leukemia.

Of the 60 people included in the study, 18 of them experienced complete remission or complete remission with partial recovery of peripheral blood counts (CR/CRh) for a little over nine months after treatment.

The results were also published in a study in the journal Nature.

Nucleophosmin mutant (mNPM1) acute leukemia is a type of acute myeloid leukemia (AML) — a cancer of the blood cells. Although AML can happen at any age, it is most common in people over the age of 45.

The mNPM1 acute leukemia occurs when the nucleophosmin (NPM1) gene in the body becomes mutated. About 30% of all cases of AML are caused by an NPM1 gene mutation.

KMT2A-rearranged (KMT2Ar) relapsed/refractory (R/R) acute leukemia occurs from a mutation of the KMT2A gene. KMT2Ar acute leukemia can present as either AML, acute lymphoblastic leukemia (ALL) or mixed phenotype acute leukemia (MPAL).

Previous research shows KMT2Ar acute leukemia to have high levels of chemotherapy resistance and relapse.

“Combined, (NPM1 mutant and KMT2Ar acute leukemias) occur in about 40% of patients with acute leukemia,” Dr. Eytan M. Stein, chief of Leukemia Service and director of the Program for Drug Development in Leukemia in the Division of Hematologic Malignancies at Memorial Sloan Kettering Cancer Center, and senior corresponding author of this study, told Medical News Today.

“The outcomes of patients with acute leukemia with these genetic abnormalities, especially when relapsed or refractory to treatment, (are) very poor — median overall survival is measured in months. New therapies are desperately needed to give these patients a meaningful therapeutic option,” he added.

In KMT2Ar acute leukemia, the KMT2A genes make fusion proteins that need to interact with a specific protein called menin in order for cancer to grow.

Additionally, mNPM1 acute leukemia is also dependent on specific genes and has been shown to be affected by the menin-KMT2A interaction.

Syndax Pharmaceuticals also recently released another study further confirming the dependency of mNPM1 and KMT2Ar acute leukemias on the menin-KMT2A interaction.

And previous research shows that menin inhibitors can help in the treatment of acute leukemia.

Dr. Stein explained that revumenib works by blocking the interaction between two proteins — menin and the MLL protein complex.

“Blocking this interaction allows the abnormal myeloid blasts to ‘differentiate’ into healthy adult neutrophils. It is a very different way of treating leukemia. Instead of killing leukemia cells, we are transforming these cells from malignant to non-malignant.”
— Dr. Eytan M. Stein

For this study, Dr. Stein and his team administered revumenib to 60 people with either mNPM1 or KMT2Ar acute leukemia. All participants had been heavily pretreated with about four prior therapies and 46% of them had previously received a stem cell transplant.

Upon analysis, researchers found 30% — or 18 of the study participants — experienced a CR/CRh with a median duration of CR/CRh response of 9.1 months. And 78% of those 18 participants — or 14 of them — attained measurable residual disease (MRD) negativity.

“Most drugs that are oral targeted therapies don’t lead to MRD negativity, let alone a rate of MRD negativity of nearly 80%! We hope this translates into better outcomes for patients,” Dr. Stein said.

The phase 1 clinical trial also included data from 68 people to evaluate the safety of revumenib. According to researchers, the medication was well-tolerated by study participants and no participants stopped taking the therapy due to treatment-related adverse effects.

“The robust clinical dataset from a heavily pretreated relapsed/refractory patient population demonstrates that revumenib monotherapy was associated with encouraging clinical benefit, including deep molecular remissions and durable responses, with minimal toxicities,” says Dr. Ghayas C. Issa, assistant professor in the Department of Leukemia in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center.

Dr. Issa is the first author of this study and also a corresponding author.

While Dr. Stein told Medical News Today that he hoped revumenib would be available as soon as possible for doctors to prescribe, he said it would hopefully become available in the next one to two years.

“We want to complete the Phase 2 portion of this study and do further studies where revumenib is combined with standard-of-care chemotherapy in patients with newly diagnosed AML with KMT2Ar and NPM1 mutations,” he said when asked about the next steps for this research.

“We also want to investigate whether this agent works in other subsets of patients with acute leukemia,” he added.