A next-generation sequencing (NGS) assay may improve early identification of patients with monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) who are at high risk of developing AL amyloidosis, according to data presented at the Association for Molecular Pathology (AMP) annual meeting. The research suggests that this method can streamline the detection of clonal immunoglobulin lambda sequences without the need for CD138 cell selection, potentially allowing earlier interventions.

The study was conducted by a team from Columbia University Irving Medical Center in New York City and Tufts University Medical Center in Boston. The team applied NGS to both bone marrow mononuclear cells (MNCs) and CD138-selected cells from 26 patients with MGUS or SMM. The assay identified clonal populations in 25 of 26 unselected MNC RNA samples (96.1%) and 24 of 26 CD138-selected samples (92.3%). Concordance between NGS and Sanger sequencing was high, with 21 of 23 cases (91.3%) showing agreement in clonal identification. In one instance, NGS detected a clonal population that Sanger sequencing on CD138-selected cells had failed to identify, illustrating the sensitivity advantage of the newer method.

The findings highlight both the feasibility and reliability of NGS for evaluating MGUS and SMM specimens. By bypassing CD138 selection, the approach reduces sample processing requirements and may accelerate the assessment of patients at risk for AL amyloidosis. The high concordance with Sanger sequencing also reinforces NGS as a valid alternative for routine clinical assessment.

The study’s authors note that early detection of clonal IG lambda populations could guide monitoring and intervention strategies, potentially preventing progression to systemic amyloidosis. As NGS becomes increasingly integrated into clinical laboratories, this method could provide pathologists with a streamlined and sensitive tool for identifying high-risk patients in hematology and oncology settings.