Screening for AL Amyloidosis in Smoldering Multiple Myeloma
Summary
In this multicenter study, we will recruit 400 patients 40 years of age or older at 15 centers with a diagnosis of smoldering multiple myeloma (SMM), a group of patients for whom standard of care is observation not treatment. The main goal of this study is to screen for the diagnosis of light-chain amyloidosis (AL) before the onset of symptomatic disease and to develop a training set for a likelihood algorithm.
Detailed description
This study is based on results from two prior studies in which 4 of 36 patients with SMM and none of 14 patients with MGUS were found to have AL. The hypothesis that we test with this protocol is that patients with (1) a pre-existing diagnosis of SMM, (2) free light chain (FLC) abnormalities, (3) IGLV genes associated with AL,(4) t(11;14) or gain 1q, and (5) NT-proBNP \> 332pg/mL will have undiagnosed AL or risk of progression to AL. We will study the potential for SMM, the FLC screen, AL-related IGLV gene use, t(11;14) or gain 1q cytogenetic abnormalities, and NT-proBNP \> 332pg/mL to be the variables in a likelihood algorithm for AL.
Outcome measures
Primary
Creating a network to enroll patients on a collaborative study requiring marrow and blood specimens, to collect data for a training set of likelihood statistics and to plan a future validation study.
With a 15-center network covering 12 states and almost 45% of the US population, we will evaluate 400 SMM patients \> 40 years old who pass FLC criteria using standard of care tests including NT-proBNP and clinical marrow specimens evaluated for the presence of t(11;14) and gain1q. Marrow cells will be processed by NGS for clonal IGLV gene identification. With the training data obtained, we will use existing statistical modeling techniques to generate a statistical algorithm for identifying undiagnosed cases of AL and assessment of risk of AL, and to plan a validation study testing the training model. We will also investigate a role for the novel biomarker clusterin (Clu) as an indicator of risk of AL in SMM patients; preliminary work indicates that Clu is significantly lower in AL than in SMM patients.
Time frame: 5 years
Validating an NGS assay that identifies IGLV genes in clonal plasma cells
All subjects will have their clonal IGLV genes identified by NGS enabling the creation and validation of a laboratory developed test in a precision medicine laboratory that is certified under regulations of the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Approval for this laboratory developed test for both κ and λ IGVL genes will permit providers, patients and researchers to use the test in decision-making to care for monoclonal gammopathy patients. We will also investigate the exploratory objective of defining the alterations in sequence in AL and non-AL FLC derived from the same IGLV germline gene.
Time frame: 5 years
Eligibility criteria
Study locations (13)
University of Alabama Hospital
Birmingham, Alabama, 35233
Cedars-Sinai Medical Center
Los Angeles, California, 90048
University of California, San Francisco
San Francisco, California, 94143
Cleveland Clinic Florida, Weston Hospital
Weston, Florida, 33331
Tufts Medical Center
Boston, Massachusetts, 02111
Columbia University Irving Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Atrium Health Levine Cancer Institute
Charlotte, North Carolina, 28204
UNC Lineberger Comprehensive Cancer Center
Durham, North Carolina, 27705
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
UT Southwestern, Harold C. Simmons Comprehensive Cancer Center
Dallas, Texas, 75390
University of Utah, Huntsman Cancer Hospital
Salt Lake City, Utah, 84112
VCU Medical Center
Richmond, Virginia, 23219
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