New FDA-approved test can ID leukemia patients for Revuforj

FISH probe kit quickly identifies KMT2A gene defects in blood cancer

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by Steve Bryson, PhD |

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The U.S. Food and Drug Administration has approved a new rapid diagnostic test to identify patients with treatment-resistant acute leukemias who may benefit from the oral therapy Revuforj (revumenib). The test is specifically designed for individuals, 1 year and older, whose cancer is driven by a chromosomal defect known as a KMT2A gene rearrangement.

The new diagnostic, the CytoCell KMT2A Breakapart FISH Probe Kit PDx, detects the clinically relevant gene defect using an accessible, rapid-turnaround test. Developed by OGT, the tool helps doctors quickly identify patients who may be eligible for Syndax‘s Revuforj treatment.

“The development and subsequent authorization of this new [companion diagnostic] is an important demonstration of the skill and commitment of our clinical scientists and regulatory specialists to deliver safe and effective diagnostics for patients with one of the most devastating forms of leukemia,” Leila Luheshi, PhD, vice president of pharma partnering at OGT, said in a company press release.

Acute leukemias are a type of blood cancer caused by genetic changes in immature blood-forming cells in the bone marrow. These changes lead to uncontrolled growth of abnormal cells that crowd out healthy blood cells. The main types are acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and mixed-phenotype acute leukemia (MPAL).

Some adults and children with acute leukemias carry a genetic defect known as a KMT2A gene translocation. This is a DNA error where a part of one chromosome breaks and fuses with another.

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Prevalence of the KMT2A gene defect

KMT2A rearrangements (KMT2Ar) are common in acute leukemias, particularly in infants. They can be detected in about 70%-80% of infants and 5%-10% of older children and adults with ALL, and in more than 50% of infants and up to 10% of adolescents and adults with AML. KMT2A rearrangements are also seen in MPAL.

More than half of those with KMT2A-related acute leukemias will relapse after receiving standard first-line therapies, with a median survival of less than one year. For those who received three or more lines of treatment, the median survival is less than three months, with 5% achieving complete remission.

“Accurately identifying acute leukemia patients with KMT2Ar is a key factor in selecting appropriate therapeutic options for a group of patients who have traditionally had a very poor prognosis,” said Adrian Smith, CEO of OGT.

Revuforj is designed to disrupt the interaction between KMT2A-encoded proteins and a protein called menin. This interaction is what fuels the development of blood cancer. The medication is expected to slow the abnormal cell growth associated with acute leukemias.

The KMT2A Breakapart FISH Probe Kit PDx is a genetic analysis test (known as a FISH test) that can detect defects in the KMT2A region in bone marrow samples from individuals with acute leukemia who have KMT2A rearrangements.

“Our strong foundation in haematology diagnostics has been a key factor in our success bringing the KMT2Ar [companion diagnostic] to market,” said Steve Chatters, OGT’s executive vice president of regulatory and medical affairs. “We have decades of experience developing regulated FISH products.”

The FISH results should be interpreted and reported by a qualified specialist and are not intended to monitor residual disease activity.

“We are optimistic the authorization of OGT’s [companion diagnostic] will help this underserved patient group benefit from developments in precision oncology,” Smith added.