CGI NGS Panel Changes the Paradigm for Multiple Myeloma

Written by: Anna Israyelyan, MD, PhD
Manager, Biopharma Solutions

Published on:
November 14th, 2017

Anna Israyelyan, MD, PhD
Dr. Israyelyan joined CGI in 2015. She has over 15 years of extensive cancer research and management experience in industry and academia covering wide range of medical areas, including basic, translational, and clinical research. Anna is an active member of the American Society of Hematology (ASH), the American Association for Cancer Research (AACR), and American Association for the Advancement of Science (AAAS). Dr. Israyelyan has a scientific advisory role with matrix management of scientific, technical, and operational aspects related to various biopharma projects and collaborations involving biomarkers in solid tumors and hematologic malignancies.

Focus::Myeloma™ replaces the multi-faceted, multi-modality complexity of current multiple myeloma diagnostics to one NGS assay, eliminating need for multiple tests while providing more accurate, timely, and cost-effective prognostic insights

Focus::Myeloma™ is CGI’s state-of-the-art, CLIA-validated disease-specific NGS test that enables deeper, more detailed evaluation of multiple myeloma (MM) patients for routine clinical management and clinical trials. The test is being used to power several high profile biopharma clinical trials and is now available for use in the clinic.

Focus::Myeloma™, a custom targeted 89-gene NGS panel, was developed by Oncospire Genomics™ (Oncospire™), CGI’s joint venture with Mayo Clinic, utilizing the extensive expertise of a leading team of MM researchers at Mayo Clinic, directed by Dr. Keith Stewart and Dr. Leif Bergsagel.  Panel development was guided by over 300 publications on MM, which have essentially defined the genetic landscape of the disease [1-6]. Launched in 2013, Oncospire™ was established to focus on developing and commercializing NGS panels as gold standards for areas of critical unmet need in oncology, including MM, a disease desperate for improved diagnostic, patient management and treatment selection strategies.


RELEVANT GENES/PATHWAYS/ACTIONABLE MUTATIONS COVERED BY FOCUS::MYELOMA™
  • Recurrently mutated MM genes: NRAS, KRAS, DIS3, TP53, RB1, etc.
  • Actionable genes: BRAF, RAS, IDH1/2, FGFR3, AKT, etc.
  • Pathways: NF-kB, MAPK, IL6-JAK-STAT, cell cycle, MYC, etc.
  • Drug Resistance: IMiDs, Proteasome inhibitors, Glucocorticoid
  • IgH, IgK, IgL and MYC loci, screening for structural abnormalities (not yet validated clinically but can report in RUO mode)


While many cancer incidence rates have declined over time, MM incidence rates continue to rise.

In the last few decades, overall myeloma incidence has increased nearly 1 percent per year [7]. MM is characterized by the clonal expansion of malignant plasma cells within the bone marrow. It is the 2nd most common hematological malignancy in the U.S. (after non-Hodgkin lymphoma) and 14th most common cancer overall, constituting 1% of all cancers and 15% of hematological malignancies. There are over 30,000 estimated new cases of MM in 2017 with 12,590 deaths in U.S. [8]. There are close to 300 open MM clinical trials in U.S. recruiting patients currently [9].

Encompassing comprehensive mutation detection (recurrently mutated and actionable genes), and providing detailed information on copy number variations (CNV) in all chromosomes, assessing chromosomal ploidy and genes associated with drug resistance and actionable pathways, this important new test can improve early detection, risk stratification, and disease monitoring in MM.

Additionally, the panel is designed to detect key translocations (including IgH, IgK, IgL, MMSET, and MYC) and clonal architecture – components under clinical validation currently – which will enable better prognostication of patients with already confirmed disease, allowing better risk assessment, prognostication, and evaluation of clonal heterogeneity and, as a result, better therapeutics selection. Lastly, it provides valuable insight on rational drug combinations and lead optimizations of the investigational compounds in clinical trials.

The current testing paradigm for MM requires multiple tests and various platforms, oftentimes requiring multiple biopsies.  Even still, current diagnostic work-ups often result in discordant results and diagnostic/prognostic uncertainty. And, no comprehensive genomic panel exists for MM…until now.

Focus::Myeloma™ is the only NGS panel of its kind, set to replace testing complexity with one comprehesive NGS-based panel, offering greater certainty and reduced complexity of diagnosis but also earlier, more accurate, and cost-effective prognostic predictions.

In short, Focus::Myeloma™ combines three tests in one, covering mutations, translocations, and copy number changes. It generates relevant information about actionable targets, drug resistance pathways, and clonal evolution of MM. We’re already working on future versions of the test, which will provide greater insight on clonal heterogeneity and structural aberrations of the disease.

The update and early feedback for Focus::Myeloma™  far surpassed our expectations.  Please send me an email to learn more or discuss how this panel can be integrated into your trial design.


[1] Fonseca R, et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res. 2004 Feb 15;64(4):1546-58.

[2] Debes-Marun CS, et al. Chromosome abnormalities clustering and its implications for pathogenesis and prognosis in myeloma. Leukemia. 2003 Feb;17(2):427-36.

[3] Avet-Loiseau H, et al. Prognostic significance of copy-number alterations in multiple myeloma. J Clin Oncol. 2009 Sep 20;27(27):4585-90. doi: 10.1200/JCO.2008.20.6136. Epub 2009 Aug 17.

[4] Smetana J, et al. Incidence of cytogenetic aberrations in two B lineage subpopulations in multiple myeloma patients analyzed by combination of whole-genome profiling and FISH. Neoplasma. 2014;61(1):48-55.

[5] Chapman MA, et al. Initial genome sequencing and analysis of multiple myeloma. Nature. 2011 Mar 24;471(7339):467-72.

[6] Chesi M and Bergsagel PL. Molecular pathogenesis of multiple myeloma: basic and clinical updates. Int J Hematol. 2013 Mar;97(3):313-23.

[7] A snapshot of myeloma. National Cancer Institute. http://www.cancer.gov/research/progress/snapshots/myeloma (Accessed on 6-22-2017)

[8] SEER Stat Fact Sheets: Myeloma. Surveillance, Epidemiology, and End Results Program, National Cancer Institute. https://seer.cancer.gov/statfacts/ (Accessed on 6-22-2017)

[9] ClinicalTrials.gov. A service of the U.S. National Institutes of Health. https://clinicaltrials.gov (Accessed on 6-22-2017)

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