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 mastocytosis (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 tryptase 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 SM and therefore had relatively low serum tryptase levels and borderline bone marrow mast cell 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.
