Background: Early diagnosis of systemic light-chain amyloidosis (AL) is needed because 25% of patients die within months of diagnosis. In patients with monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM) of the λ isotype, we explored the use of 2 screening variables: a free light chain difference of 23mg/L between λ and k and presence of IGLV genes that occur more frequently in AL.
Methods: Patients contacted us and we sent HIPAA release and consent forms for discussion by phone. Their physicians were not involved. We enrolled patients with λ MGUS or SMM who met the FLC criteria with no prior biopsies showing amyloid. They sent us blood or marrow specimens for IGLV gene amplification by RT-PCR; we also assessed the feasibility of next generation sequencing (NGS) for IGLV genes. We informed patients and their physicians of results suggesting further evaluation for AL.
Results: We enrolled 21 patients, 19 SMM and 2 MGUS, receiving blood (n=21) or marrow (n=5) specimens. We identified IGLV genes in 86% (18/21) of cases. Four of the 18 IGLV genes were not AL-related and 3 of these 4 progressed to myeloma requiring therapy; the 4th was screened for amyloid and was negative. Fourteen patients with AL-related genes had comprehensive evaluations and two with SMM had AL. RT-PCR and NGS identified the AL-related LV2-14 in those two and also the monoclonal IGLV genes from all of the marrow but not the peripheral blood samples.
Conclusion: We concluded that these variables may be useful in screening for AL in λ MGUS and SMM patients and acquired support for a small multi-center study employing marrow samples only.
Keywords: AL amyloidosis; IGLV genes; monoclonal gammopathies; next generation sequencing.