The overall survival (OS) and progression-free survival (PFS) of this small group of patients were found to be superior to those of the patients with a traditional secretory myeloma phenotype (36 vs 23 months)

The overall survival (OS) and progression-free survival (PFS) of this small group of patients were found to be superior to those of the patients with a traditional secretory myeloma phenotype (36 vs 23 months).23 A possible hypothesis for this could be that there is a lower frequency of high-risk genetic alterations in the non-secretory patients, which allows Daun02 their improved outcomes respect to patients with IgG, IgA, or light chain myelomas.16 In 1986, Smith et al. to depict a new definition of nonsecretory myeloma that deserves a peculiar work up and different response evaluation and, may be, a different therapeutic approach. strong class=”kwd-title” Keywords: Non-secretory myeloma, free light chain, myeloma subtype Introduction Multiple myeloma (MM) is a malignancy Mouse monoclonal to Ractopamine of plasma cells defined by infiltration of bone marrow, and presence of CRAB feature (skeletal lesions, anemia, bone pain, renal insufficiency, hypercalcemia) as well as 3 specific biomarkers: clonal bone marrow plasma cells 60%, serum free light chain (FLC) ratio 100 (provided involved FLC level is 100 mg/L), and more than one focal lesion on magnetic resonance imaging (MRI).1C2 In the USA this hematologic malignancy accounts for approximately 10% of all hematologic neoplasm and 1% of all malignant disease, being twice as common in African-Americans compared with Caucasians and lowest among the Chinese and Japanese.1,2 In Italy data are similar, MM accounting of 1% of all cancers and 13% of all hematologic malignancies.3 MM cells represent the neoplastic counterpart of normal plasma cells, and thus the hallmark of most neoplastic plasma cells is the persistent production of clonal immunoglobulin, albeit completely non-functional, either complete (heavy and light chain) or as part of immunoglobulins (heavy chain or light chain). The availability of this protein in the blood or urine for quantitative assessment using serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), or the serum free light chain assay allows easy monitoring of response in most cases of myeloma.4C5 Monoclonal component (MC) typically can be detected in serum and/or urine as: high concentrations of Daun02 a full Ig molecule consisting of heavy and light chains bound together; elevated levels of the complete Ig molecule plus high concentrations of light chains unbound to heavy chain (free light chains [FLCs]); primarily FLC in the presence of minimal amounts or even no complete Immunoglobulin (Ig) whatsoever which is rare; a fourth entity, characterized by the absence of detectable MC either in the serum or the urine, represents a very small subset of the myeloma population. The incidence of these non-secretory multiple myelomas (NSMMs) ranges from 3% to 5% of the total MM population.6C8 However, advances in the detection of serum FLCs have demonstrated that most of these previously defined NSMMs are probably oligo secretors,9 namely producing primarily or solely serum FLC in the absence of heavy chain. Thus, the proportion of true NSMM, meaning MM that secretes no measurable monoclonal heavy or light chains at all, is closer to 1C2% of all MMs.1,10 Non-secretory myeloma Daun02 is classically defined as clonal bone marrow plasma cells 10% or biopsy proven plasmacytoma, evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically hypercalcemia, renal insufficiency, anemia, or bone lesions, and lack of serum and urinary monoclonal protein on electrophoresis and immunofixation.8C9 Clinically, patients who present with true non-secretory disease at diagnosis behave differently from patients who present with the oligo-secretory disease, as well as from those who progress from having secretory disease at diagnosis to oligo-secretory or non-secretory disease at the time of relapse. In this article, we review all the information available on this particular entity trying to outline a possible definition of different subsets of non-secretory myeloma. Biological Basis Non-secretory myeloma patients Daun02 can be divided into several groups. The true non-secretory myeloma should be considered only the group of non-producers patients, whose tumors have a defect in immunoglobulin synthesis, resulting in no measurable protein in the blood or urine, although they still have a significant plasma cell burden in the bone marrow and evidence of end-organ damage.11 In these individuals, even the use of the FLC assay will not reveal measurable disease as currently defined.12 The next category of nonsecretory myeloma individuals consists of those instances whose neoplastic plasma cells produce an altered MC but have problems in secretion. The exact mechanisms that prevent either production or secretion of monoclonal Ig by NSMM remain poorly recognized. One hypothesis argues that true NSMMs arise from a consecutive loss of secretion, firstly of weighty chains and then light chains.13 It has been demonstrated in vitro that a sole amino acid substitution inside a light chain can potentially block secretion outside the cell and that a mutation in the immunoglobulin gene can account for the lack of secretion in a patient with non-secretory myeloma.14 On the other hand, individuals presenting only immunoglobulin light chains in serum and urine, and then affected by light chain MM, never displayed a functional IgH recombination.15 The absence of.