A Diagnostic Screening Trial Seeking AL Amyloidosis Very Early
Condition: Plasma Cell Dyscrasia; Monoclonal Gammopathy
MeSH terms: Immunoglobulin Light-chain Amyloidosis; Multiple Myeloma; Neoplasms, Plasma Cell; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance; Amyloidosis
Study type: Observational

Summary: 
      This protocol seeks to enroll smoldering multiple myeloma (SMM) and monoclonal gammopathy of
      undetermined significant (MGUS) patients with λ light chain (LC) involvement, a group of
      patients for whom standard of care is observation not treatment. Patients with SMM and MGUS
      have a precursor plasma cell disorder from which light chain amyloidosis (AL) can evolve. In
      this trial, enrolled subjects will have blood and if available bone marrow cells evaluated by
      molecular testing to determine their clonal λ LC variable region (VL) germline gene. Seventy
      percent of AL cases involve just 7 germline donors, 5 of which are λ germline donors. The
      hypothesis that will be tested with this protocol is that the presence of AL germline genes
      associated with AL in patients with a pre-existing diagnosis of λ SMM or λ MGUS indicates the
      presence of AL or risk of progression to AL.
    

Detailed description: 
      In this trial up to 200 patients with either λ light chain (LC) monoclonal gammopathy of
      undetermined significance (MGUS) or λ LC smoldering multiple myeloma (SMM) with a κ::λ LC
      ratio < 0.26 and whose λ minus κ LC difference (dFLC) is greater than 23 mg/L will be
      recruited. Heavy chain type will not affect patient eligibility as long as the involved LC is
      λ type.

      Patients may learn about the trial through internet advertisements and contact the data
      manager to receive the study's enrollment documents. Patient recruitment will be open to all
      eligible patient within the United States. Informed consent may be obtained in person or by
      phone. After the patient has completed a HIPPA release form, the patient's physician will be
      contacted and informed of the patient's consent to this study and will be asked to provide
      medical records for screening. If the patient is found eligible, the patient and physician
      will be informed of the required samples for the protocol, which include peripheral blood and
      marrow aspirate, if available, with both taken during routine clinical procedures. Prepaid
      FedEx boxes will be provided by the study to ship research samples to Tufts Medical Center
      for remote patients.

      Both the peripheral blood and marrow samples will be tested for the presence of variable
      region (VL) germline genes in our Tufts Medical Center laboratory. In addition, plasma
      isolated from the peripheral blood sample (as well as the corresponding identified germline
      gene) will be sent to the laboratory of Dr. Jonathan Wall at the University of Tennessee for
      assay analysis. The assay will seek to distinguish the presence of amyloidogenic vs.
      non-amyloidogenic light chains. Germline gene results from Tufts Medical Center will be
      shared with patients and their physicians; however, University of Tennessee assay analysis
      will not be shared due to its experimental nature.

      The analysis of this trial will be based on the frequency with which enrolled MGUS and SMM
      patients are found to have genes associated with light chain amyloidosis (AL), are found to
      have asymptomatic AL or symptomatic AL, or progress to AL. The diagnosis of AL is a tissue
      diagnosis. If amyloidosis is suspected at any time during a subject's participation, their
      physician will be contacted and given recommendations regarding diagnostic tests and disease
      staging.
    

Observational model: Other
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        This study will enroll up to 200 MGUS and SMM patients with λ LC involvement with dFLC >23
        mg/L and κ:: λ free LC ratio <0.26. Subjects must be able to share their medical records
        and ship bone marrow and blood samples to our laboratory.
      
Biospecimen description: 
      Bone marrow and peripheral blood samples.