Focus::Lymphoma™ | Comprehensive, Clinically Actionable, and Disease-Specific Proprietary NGS

Written by: AndrewLincoln

Published on:
May 30th, 2017


It’s been a year since the launch of our CLIA-validated proprietary Focus::Lymphoma panel.  To date, it remains the most comprehensive and clinically actionable disease-specific lymphoma panel in precision medicine.

Since its introduction into the clinical trial setting in early 2016, Focus::Lymphoma has been utilized to power academic studies and several clinical trials, as well as the clinical setting [1, 2]. By focusing on Diffuse Large B-cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), and Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL), the panel has allowed for a more comprehensive coverage of genes contributing to the growth and development of improved precision testing in the marketplace.

Focus::Lymphoma enables the targeted sequencing of 220 genes for the identification of single nucleotide changes (mutations) as well as insertions/deletions. Analysis and reporting can be customized to report specific indications and genes of interest, providing clinically actionable information to determine treatment options for patients with various forms of mature B-cell lymphomas. The high quality panel has undergone rigorous validation. While disease specific, the panel is quite comprehensive in terms of the mutations covered, and can be an important addition to the clinical/pathologic workup of patients with various forms of B-cell lymphomas, as confirmed by physicians and researchers familiar with the panel.

The 220 genes in the panel were selected based on frequency of mutation, theranostic, diagnostic, and prognostic associations, as well as their potential to interact with known dysregulated pathways in B-cell lymphoma.

Altogether, the panel encompasses genes associated with outcomes, actionable targets, related to biologically significant pathways, and/or frequently mutated in mature B-cell lymphomas. Inclusion of targets associated with both approved and clinically late-stage therapies into Focus::Lymphoma has been prioritized aiming to provide the insight necessary to evaluate future combination regiments. Uniquely, the panel represents enriched pathways such as BCR/PI3K/WNT signaling, and focal adhesion, and those associated with resistance to inhibitors of these pathways. Specifically, Focus::Lymphoma covers the reported alterations known to confer resistance to targeted drugs, such as ibrutinib and venetoclax. Those include mutations of PLCG2, BTK, and BCL2 family. The following schematic depicts the mechanisms of resistance to ibrutinib and venetoclax targeted therapies and potential bypass strategies.

Mechanisms of resistance to targeted therapies and potential bypass strategies. Known and hypothesized mechanisms of resistance to ibrutinib (A) and venetoclax (B) are outlined along with potential mechanisms to overcome resistance. *Unknown mechanisms, which may have the potential to respond to other targeted therapies or chemoimmunotherapies, but may also be considered for salvage with reduced-intensity allogeneic stem cell transplantation or CAR T-cell therapies.

Mutations affecting epigenetic and transcriptional modifiers now appear to be an almost universal feature of B-cell lymphomas. Large-scale disruptions of DNA methylation and histone modification patterning emerged as a hallmark of these diseases. Many studies are trying to understand the nature of the lymphoma epigenome and the biochemical and biological effects of mutant epigenetic factors, and the development of genuine targeted therapy drugs is underway. Agents targeting mutated or aberrantly functioning transcription factors, chromatin modifying enzymes and epigenetic reader proteins, including EZH2, MLL2, p300 (EP300), BCL6, and TET2, are in clinical studies and hold the promise to significantly advance the treatment of B-cell lymphomas with less toxicity to the normal immune system and other tissues. All the mentioned targets are covered by Focus::LymphomaTM. Importantly, some of these targets, though frequently mutated in B-cell lymphomas, are not covered by other commercial platforms.

Many oncologists find CGI Focus::Lymphoma™ panel very impactful for their patients:

We recently treated a relapsed patient with a NRAS Q61R mutation in his tumor cells, identified using the CGI Focus::Lymphoma™ panel and were gratified to see a response with MAP kinase targeting drugs even when his disease had progressed after multiple lines of chemotherapy,”  said Samir Parekh, M.D., Associate Professor at Mount Sinai School of Medicine in New York.             

Drop me an email to learn more about Focus::Lymphoma. I’d be happy to schedule time to help evaluate and discuss how this panel can be integrated into your clinical trial biomarker strategy and meet your drug development needs.

[1] Siddiqi IN, et al. Characterization of a variant of t(14;18) negative nodal diffuse follicular lymphoma with CD23 expression, 1p36/TNFRSF14 abnormalities, and STAT6 mutations. Mod Pathol. 2016 Jun;29(6):570-81.