Ultrasensitive duplex sequencing could improve the diagnosis of indolent systemic mastocytosis (SM) in patients with low variant allele frequencies (VAF), according to an interview recently published in OncLive.
The interview referred to the phase 2 PIONEER study, which assessed the safety and efficacy of avapritinib in patients with SM.
What is SM?
Systemic mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults. (SM) is a rare hematological disease characterized by mast cells that are overactive and accumulate in different parts of the body such as the bone marrow, liver, spleen, gastrointestinal tract and lymph nodes.
The study used duplex sequencing to identify KIT mutations in patients that appeared to be negative with standard methods, according to Tracy I. George, chief scientific officer and president of the Innovation Business Unit at ARUP Laboratories and a professor of pathology at the University of Utah’s Spencer Fox Eccles School of Medicine.
Read more about SM testing and diagnosis
“By doing [ultrasensitive duplex sequencing], especially in peripheral blood, which is much easier to access, we’re going to increase diagnostic sensitivity, [thereby] identifying more patients with ISM who can then qualify for therapy,” George said.
Current standard techniques for SM diagnosis, such as droplet digital PCR (ddPCR) and tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. serum levels, can produce false negatives in a significant proportion of patients, as the KIT mutations have low levels in the blood of most patients.
In the PIONEER study, ddPCR detected KIT mutations in approximately 85% of patients, while duplex sequencing successfully detected them in more than 96% of patients.
Many of the patients included in the trial were in the early stages of indolent SMIndolent SM A subtype of nonadvanced SM caused by the abnormal accumulation of mast cells in the bone marrow and other organs. Indolent SM accounts for around 90% of SM cases. and therefore had relatively low serum tryptase levels and borderline bone marrow mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. burden, George said. This highlighted the potential of duplex sequencing to diagnose SM in patients with low disease burden in the early stages.
Although duplex sequencing was already validated in a clinical trial, George emphasized the need for real-life testing outside clinical trial settings. The technique can also be of value for diagnosing other diseases, such as myeloproliferative neoplasms, she added.
“The significance is that we’re able to detect more patients with the KIT D816V mutation,” George said. “If we review what’s out there in the literature, we find that the detection of the KIT mutation is the single best criterion that we have for detecting systemic mastocytosis.”
Sign up here to get the latest news, perspectives, and information about SM sent directly to your inbox. Registration is free and only takes a minute.
