Interim Analysis Of The Mmrf Commpass Trial, a Longitudinal Study In Multiple Myeloma Relating Clinical Outcomes To Genomic and Immunophenotypic Profiles

• Published in: Blood 2013-11, Vol.122 (21), p.532-532
• Main Authors: Keats, Jonathan J, Craig, David W, Liang, Winnie, Venkata, Yellapantula, Kurdoglu, Ahmet, Aldrich, Jessica, Auclair, Daniel, Allen, Kristi, Harrison, Beverly, Jewell, Scott, Kidd, Pamela G., Correll, Mick, Jagannath, Sundar, Siegel, David S., Vij, Ravi, Orloff, Gregory, Zimmerman, Todd M., Capone, Walter, Carpten, John, Lonial, Sagar
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V122.21.532.532

The Multiple Myeloma Research Foundation (MMRF) CoMMpass trial is the cornerstone of the MMRF Personalized Medicine Initiative. The accrual goal is 1000 patients with newly-diagnosed active multiple with sufficient tumor material for the comprehensive analysis of each tumor genome. Each eligible patient will be followed from initial diagnosis longitudinally for a minimum of 8 years. Additional tumor samples will be collected and comprehensively analyzed when possible for each patient at time of suspect CR, recurrence or progression of disease. The clinical study (NCT0145429) opened in July 2011 and now includes 56 sites in the US and Canada that have enrolled over 300 patients as of Aug. 1, 2013. The frontline treatments permitted in this study include current standard of care therapies containing a proteasome inhibitor, an IMiD or both. The comprehensive analysis of each tumor and matched normal genome involves; Long-Insert Whole Genome Sequencing (WGS) to identify somatic copy number alterations and structural changes, Whole Exome Sequencing (WES) to identify somatic single nucleotide variants and indels, and RNA sequencing (RNAseq) to define transcript expression levels and fusion transcripts. In addition, BRAF pyrosequencing and immunophenotyping analysis are being done in CAP-CLIA certified labs. An extensive, open-access, public clinical and molecular database, the CoMMpass Researcher Gateway (RG) (https://research.themmrf.org), is being developed to facilitate the rapid dissemination of the results and provides the myeloma community with a mechanism to analyze the results. The clinical endpoints and outcomes also include Quality of Life measures and health care resource utilization. An initial interim analysis on the first 178 cases has just been completed and made publicly available through the CoMMpass RG. At the molecular level, BRAF analysis on this serial sample set of newly diagnosed patients identified V600E mutations at rate of 5.7%, confirming our previous observations from a mixture of non-consecutive treated and untreated patient samples in our previous genomic efforts. The flow cytometry panel was designed to provide a comprehensive immunofingerprint of each patient that could be used for minimal residual disease monitoring and to monitor potentially therapeutic options; MS4A1/CD20, CD52, KIT/CD117, and FGFR3. These studies have identified tumors which are 100% positive for these actionable antigens at frequencies of; 16.0% for CD20, 5.7