Non-secretory multiple myeloma: from biology to clinical management

Abstract

Multiple myeloma (MM) is the second most common hematologic malignancy in the US. It is typically characterized by production of large amounts of defective immunoglobulin (Ig). Diagnosing MM and monitoring treatment response, including eventual relapse, are largely based on sequential measurements of Ig. However, a small subset of MM called non-secretory multiple myeloma (NSMM) produces no detectable Ig. This subset of true NSMM has become even smaller over time, as the advent of the serum free light chain assay has resulted in the majority of NSMM patients being recategorized as light-chain MM – that is, MM cells that produce only the light-chain component of Ig. True forms of NSMM, meaning MM that secretes no monoclonal proteins whatsoever, constitute a distinct entity that is reviewed; definition of NSMM using current detection methods, discuss the biology underpinning NSMM development, and share recommendations for how NSMM should be managed clinically with respect to detection, treatment, and monitoring.

Nonsecretory Multiple Myeloma Presenting as Recurrent Vertebral Compression Fractures in an Older Male Patient

“…4) They demonstrated that time to progression, progressionfree survival, and overall survival prior to 2001 were similar between NSMM patients and secretory MM patients. 4) Between 2001 and 2012, the time frame during which new therapeutics were broadly introduced, there was a marked increase of overall survival in both groups. 4) However, the improvement in overall survival was greater in the NSMM group.…”

“…4,5) The definition of MM from the 2014 International Myeloma Working Group includes 10% or more clonal plasma cells in the bone marrow or biopsy-proven bony or extramedullary plasmacytoma and one or more of the seven listed criteria (hypercalcemia, renal insufficiency, anemia, bone lesions, clonal bone marrow plasma cells ≥60%, involved/uninvolved SFLC ratio ≥100 and involved SFLC concentration ≥10 mg/dL, and 2 or more focal lesions based on MRI studies of the skeleton). 6) The International Myeloma Working Group still defines NSMM as MM lacking monoclonal protein on serum or urine electrophoresis.…”

“…4) Between 2001 and 2012, the time frame during which new therapeutics were broadly introduced, there was a marked increase of overall survival in both groups. 4) However, the improvement in overall survival was greater in the NSMM group. 4) In addition, the overall survival was superior in patients with a normal baseline FLC ratio compared to that in patients with an abnormal ratio.…”

Cold Agglutinin Disease in Non-Secretory Multiple Myeloma: A Case Report

“…These are MM variants or related plasma cell diseases with measurable intracellular immunoglobulin by immunofluorescence, whereas they are not measurable extracellular components via typical testing. It has been suggested that these immunoglobulins are secreted in vesicles via budding of the cell membrane, rendering them undetectable in the serum [13].…”

3‐Bromopyruvate as a potent anticancer therapy in honor and memory of the late Professor André Goffeau

“…However, in MM, the antibodies are defective and completely nonfunctional (Gerecke et al, ; Ramsenthaler et al, ; Zhang et al, ). There are also rare forms of nonsecretory MM cells that produce only light chains of Igs (Dupuis & Tuchman, ). The hallmarks of MM are primarily end‐organ damage and the occurrence of bone lesions.…”