A newly developed assay can rapidly and accurately recognize different subtypes of diffuse large B-cell lymphoma (DLBCL), providing useful diagnostic information that could help doctors match tumors with the right treatment.
The study, titled “Determination of Molecular Subtypes of Diffuse Large B-Cell Lymphoma Using a Reverse Transcriptase Multiplex Ligation-Dependent Probe Amplification Classifier: A CALYM Study,” was published in The Journal of Molecular Diagnostics.
DLBCL is the most common non-Hodgkin’s lymphoma subtype. Depending on the cell from which the disease originates, DLBCL can be classified into germinal center B-cell-like, activated B-cell-like, and primary mediastinal B-cell lymphoma.
Because each subtype has different molecular pathways involved in disease development and progression and different outcomes, it is imperative that clinicians identify the DLBCL subtype at diagnosis. This is of particular importance for choosing the appropriate treatment approach.
“Many targeted therapies are under clinical evaluation and being able to distinguish these diseases routinely and accurately should soon become a major goal,” lead author Victor Bobée, PharmD, of the Henri Becquerel Cancer Treatment Center in Rouen, France, said in a press release.
Bobée and his team examined the gene expression profile of 70 preserved biopsies and created a DLBCL classifier that accurately identifies each subtype. The tool was then validated in more than 160 additional samples.
Based on the levels of 21 biomarkers, the assay is able to assign 85% of the samples to their respective subtype. This contrasts with the current technique, immunohistochemistry, which correctly identifies 78.8% of samples. Also, the tool allows the identification of other clinical features, such as Epstein Barr infection.
The assay was complemented with the addition of a probe that identifies a specific variant of the MYD88 gene, the most common genetic abnormality in activated B-cell-like subtype. Patients with this variation are more likely to respond to the BTK inhibitor Imbruvica (ibrutinib).
The assay only requires common laboratory reagents and equipment, making it easy to implement into routine diagnosis workflows without additional expenses.
“Because we have provided the classification algorithms, other laboratories will be able to verify our results and adjust the procedures to suit their environment,” said Philippe Ruminy, PhD, a researcher at the Henri Becquerel Cancer Treatment Center and co-author of the study.
“It is our hope that the assay we have developed, which addresses an important recommendation of the recent World Health Organization (WHO) classifications, will contribute to better management of these tumors and improved patient outcomes,” he added.
The study is part of the CALYM academic consortium, which aims to accelerate discovery and development of new treatments and tools for lymphoma.