The Multiple Myeloma Research Foundation (MMRF) CoMMpass^SM Study: A Longitudinal Study in Newly-Diagnosed Multiple Myeloma Patients to Assess Genomic Profiles, Immunophenotypes and Clinical Outcomes

Abstract 3980

The Multiple Myeloma Research Foundation (MMRF) CoMMpass^SM trial plans to analyze the tumor genome from 1000 patients with newly-diagnosed active multiple myeloma (ND-MM) from initial diagnosis over a period of 8 yrs [http://clinicaltrials.gov/ct2/show/NCT01454297]. Eligible patients include those with symptomatic MM who have not received prior therapy and provide consent for submission of paired specimens of bone marrow aspirate containing tumor cells and peripheral blood specimens for molecular analysis and biobanking. Individual tumor genomes will be sequenced to reveal the molecular and genetic changes underpinning tumor response and clinical benefit of therapies for MM and to facilitate future clinical trial designs. An extensive clinical and molecular database is being developed to facilitate association studies. The clinical endpoints and outcomes also include Quality of Life measures and health care resource utilization. The molecular database includes data from Whole Genome Sequencing, Whole Exome Sequencing and RNA sequencing comparing tumor to normal health mononuclear cells as part of the longitudinal profile of MM disease progression and clinical response in individual patients.

The clinical study opened in July 2011 and includes 55 sites in the US contributing over 180 patients as of Aug 8, 2012. The frontline treatments permitted in this study include current standard of care therapies containing a proteasome inhibitor, an IMiD or both. Screening of 1500 individuals presenting with suspected myeloma in primary care community and academic centers is expected to identify individuals with asymptomatic MGUS, SMM and active MM patients. Patients with a confirmed diagnosis of asymptomatic myeloma or MGUS will be invited to re-enroll in CoMMpass^SM Study upon conversion to active disease.

Centralized bone marrow aspirate and peripheral blood specimen processing is being conducted to support profiling of the patient samples. The workflow for biospecimens includes real time analysis of bone marrow aspirates by multiplex flow cytometry to identify patient-specific immunophenotypic markers to follow evidence of Minimal Residual Disease (MDR), recurrence of disease and emergence or expansion of new tumor cell clonal populations³. B-raf pyrosequencing and immunophenotyping are performed in CAP-CLIA certified labs and results are provided to physicians. Included in these assays are potentially actionable drug targets include the following proteins: CD52 [CAMPATH-1], CD117 [c-kit], FGFR3, B-raf ^V600E and CD20. CD138-positive tumor cells purified from BM aspirates and paired healthy cells undergo sequencing analysis comprising Shallow Whole Genome and Whole Exome sequencing and transcriptome analysis. Chromosomal alterations and ploidy will be assessed by cytogenetic and FISH analysis. Altogether, these efforts will provide an unprecedented myeloma dataset on structural and copy number variation, mutation and gene expression. Samples collected at suspected Complete Response will also be evaluated by flow cytometry using multiple markers to follow immunophenotypic changes and to monitor minimal residual disease (MRD) and clonal evolution of the tumor population over time.

The MMRF CoMMpass^SM study will comprehensively catalog genomic alterations in patients treated with standard-of-care 1st line agents at significant clinical events, such as suspected CR, recurrence or progression of disease. The knowledge base developed from CoMMpass^SM will fuel key insights into mechanisms of disease and drug response in myeloma, new drug targets and pathways, prognostic and predictive biomarkers for clinical validation and development and refine molecular classification of MM subtypes. The MMRF CoMMpass^SM Research database and Myeloma Community portal will serve as a foundation to build personalized medical care strategies for MM patients.