Prognostic Validation of the International Classification of Immunoglobulin M Gammopathies: A Survival Advantage for Patients with Immunoglobulin M Monoclonal Gammopathy of Undetermined Significance?

Abstract

Purpose: To verify the reliability of the new criteria for the diagnosis of IgM gammopathies recently proposed by an international panel of experts (Athens, 2002). Experimental Design: A retrospective series of 698 patients with IgM gammopathy was reviewed paying attention to symptoms, serum IgM concentration, bone marrow infiltration, blood cell count and clinical course. Four clinical entities can be identified: IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), asymptomatic and symptomatic Wandenström's macroglobulinemia (A-WM and S-WM, respectively), and IgM-related disorders, although this last was excluded from the study because of the scarcity of patients due to probable selection biases. The observed mortality was studied related to that expected in the general population of comparable age and sex and over an equivalent period of follow-up (standardized mortality ratio, SMR). Results: IgM-MGUS, A-WM, and S-WM shared many clinical aspects but, with respect to the general population, patients with IgM-MGUS had a slight but definite survival advantage, those with A-WM had a mortality rate equivalent to that of the general population, whereas the SMR of patients with S-WM was 5.4. Within A-WM and S-WM the SMR values did not vary significantly in relation to marrow lymphocyte counts or serum IgM concentrations. Conclusions: Our findings represent a prognostic validation of the applied diagnostic criteria for three of the four identifiable clinical entities and highlight the importance of symptoms over serum IgM concentration and marrow infiltration.

Progression in smoldering Waldenström macroglobulinemia: long-term results

“…Indeed, a study by Baldini et al demonstrated that the overall survival of SWM patients is similar to that of the general population, making it more important that these patients be recognized clinically and avoid the risks of chemotherapy. 13 Of interest, Gobbi et al previously reported that the overall survival was similar to that of the general population, 14 attributable perhaps to closer medical surveillance resulting in better care of hypertension, diabetes, and other common disorders. It is therefore in the patient's best interest to recognize this entity so that these patients are not subjected to the risks of chemotherapy until evidence of progression to symptomatic WM.…”

“…3 The criteria we use differ 2 and are based on subsequent studies. [12][13][14] We consider asymptomatic patients with an IgM M protein Ͻ 3 g/dL and lymphoplasmacytic infiltration less than 10% as IgM MGUS, and not WM. 2 Because these patients have a survival similar to the general population and require no therapy, they should not be erroneously labeled as having a malignancy.…”

“…In this study, we define the natural history of SWM, which like IgM MGUS has an indolent clinical course and must be differentiated from WM. 13,14 The diagnosis of SWM requires a serum monoclonal protein level of Ͼ 3 g/dL and/or 10% or more lymphoplasmacytic cells in the bone marrow and absence of symptomatic anemia, constitutional symptoms, hyperviscosity, symptomatic lymphadenopathy, or hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder. 2 In addition to the M spike and bone marrow infiltration, patients may have mild anemia, reduction of uninvolved serum immunoglobulins, modest reduction of serum albumin levels, or elevation of ␤ 2 -microglobulin.…”

Diagnosis and Management of Waldenström Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines

“…To date, no evidence suggests that treatment of patients with smoldering/asymptomatic Waldenström macroglobulinemia provides a survival benefit compared with patients who begin therapy once symptoms occur. 34,35 Also, no evidence shows that delaying therapy until clinical progression occurs adversely affects the subsequent response to treatment. 36 Asymptomatic patients have a better quality of life without therapy, and withholding initial therapy limits their exposure to chemotherapeutic agents and possibly prevents development of drug resistance.…”

Advances in the Diagnosis, Classification, Risk Stratification, and Management of Monoclonal Gammopathy of Undetermined Significance: Implications for Recategorizing Disease Entities in the Presence of Evolving Scientific Evidence

“…Next, the natural history of each disease cohort was determined using sound epidemiological methods. 3,8,9,11,12,[14][15][16] As a result, we clearly know how to diagnose each of these entities accurately, and we also know the outcome of patients meeting the specific disease definition to assist with management and counseling. This approach to developing disease definitions is preferable to arbitrary criteria, in which the characteristics and outcome of patients meeting such criteria are unknown.…”