Prognostic Factors for Malignant Transformation in Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma

Cesana, Clara; Klersy, Catherine; Barbarano, Luciana; Nosari, Anna Maria; Crugnola, Monica; Pungolino, Ester; Gargantini, Livio; Granata, Simonetta; Valentini, Marina; Morra, Enrica

doi:10.1200/jco.2002.20.6.1625

Cited by 165 publications

(109 citation statements)

References 31 publications

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“…The role of immunoparesis of the noninvolved isotypes had been addressed before. In MGUS, suppression of the noninvolved polyclonal isotypes was associated with a higher risk for progression into active disease 6, 29, while in smoldering myeloma discrepant findings have been reported. Pérez‐Persona et al 30 identified immunoparesis as a significant risk factor for progression and included this parameter in a risk model for patients with smoldering myeloma 31.…”

Section: Discussionmentioning

confidence: 93%

Suppression of the noninvolved pair of the myeloma isotype correlates with poor survival in newly diagnosed and relapsed/refractory patients with myeloma

Ludwig

Milosavljevic

Berlanga³

et al. 2016

American J Hematol

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Heavy light chain (HLC) assays allow precise measurement of the monoclonal and of the noninvolved polyclonal immunoglobulins of the same isotype as the M‐protein (e.g., monoclonal IgAκ and polyclonal IgAλ in case of an IgAκ myeloma), which was not possible before. The noninvolved polyclonal immunoglobulin is termed ‘HLC‐matched pair’. We investigated the impact of the suppression of the HLC‐matched pair on outcome in 203 patients with multiple myeloma, a phenomenon that likely reflects the host's attempt to control the myeloma clone. Severe (>50%) HLC‐matched pair suppression was identified in 54.5% of the 156 newly diagnosed patients and was associated with significantly shorter survival (45.4 vs. 71.9 months, P = 0.019). This correlation was statistically significant in IgG patients (46.4 vs. 105.1 months, P = 0.017), but not in patients with IgA myelomas (32.9 vs. 54.1 months, P = 0.498). At best response, HLC‐matched pair suppression improved only in patients with ≥VGPR, indicating partial or complete humoral immune reconstitution during remission in those with excellent response. Severe HLC‐matched pair suppression retained its prognostic impact also during follow‐up after first response. In the 47 pretreated patients with relapsed/refractory disease, a similar correlation between severe HLC suppression and survival was noted (22.8 vs. not reached, P = 0.028). Suppression of the polyclonal immunoglobulins of the other isotypes than the myeloma protein correlated neither with HLC‐matched pair suppression, nor with outcome. Multivariate analysis identified severe HLC‐matched pair suppression as independent risk factor for shorter survival, highlighting the impact of isotype specific immune dysregulation on outcome in multiple myeloma. Am. J. Hematol. 91:295–301, 2016. © 2015 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 93%

Suppression of the noninvolved pair of the myeloma isotype correlates with poor survival in newly diagnosed and relapsed/refractory patients with myeloma

Ludwig

Milosavljevic

Berlanga³

et al. 2016

American J Hematol

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“…Confirmamos que los pacientes con fenotipo evolving presentan un mayor riesgo de progresión a mieloma. Además, estudiamos una serie de biomarcadores que predicen conversión a MM en el MGUS 13,17 . Observamos que dichos marcadores también predicen la aparición de un fenotipo evolving.…”

Section: Discussionunclassified

“…A lo largo del tiempo, se han descrito una serie de factores que al diagnóstico estratifican el riesgo de conversión a MM en el MGUS. Así, un porcentaje elevado de CP en la médula ósea (entre 6 y 9%) o la presencia de CP circulantes (entidades que se ven raramente en el MGUS) se asocian con una mayor probabilidad de progresión 13,14 . La presencia de CP con un fenotipo aberrante también aumenta el riesgo de progresión [14][15][16] .…”

Section: Introductionunclassified

Marcadores pronósticos en pacientes con gammapatía monoclonal de significado incierto

et al. 2014

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“…The impact of the M-protein size was well-demonstrated in the largest series with longest follow-up reported thus far, in which the risk of MGUS progression at 20 years progressively increased from 14%, 25%, 41%, and 49% for a monoclonal protein higher than 0.5 g/dL, 1.5 g/dL, 2 g/dL, and 2.5 g/dL, respectively [26••]. The prognostic influence of the proportion of BMPCs has been observed in all the three series in which a bone marrow aspirate was performed and examined [7,27,28]. In almost all series, the immunoglobulin A M-protein type was associated with a significantly higher risk of malignant transformation [7,26••,27,29,30].…”

Section: Monoclonal Gammopathy Of Undetermined Significancementioning

confidence: 96%

Smoldering multiple myeloma and monoclonal gammopathy of undetermined significance

Bladé

Rosiñol²

2006

Curr. Treat. Options in Oncol.

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Smoldering multiple myeloma (SMM) consists of the presence of a serum M protein of 30 g/L or more and/or 10% or more bone marrow plasma cells (BMPCs), with no clinical manifestations or symptoms of myeloma. It accounts for approximately 10% of all myelomas, and the median time to progression to a symptomatic multiple myeloma ranges from 2 to 3 years. The main factors for progression are the plasma cell mass (M-protein size and percent of BMPCs), the spinal MRI pattern, the plasma cell proliferative index, and the variant of SMM ("evolving" vs "nonevolving"). Although treatment with thalidomide is promising (based on the results of two phase II trials), outside the context of a clinical trial, a watch-and-wait approach with clinical evaluation every 4 months is recommended until evident symptomatic disease progression occurs. Patients with monoclonal gammopathy of undetermined significance (MGUS) have a serum M protein lower than 30 g/L and a proportion of BMPCs of less than 10%, with no clinical findings or symptoms attributable to the monoclonal gammopathy. MGUS has a high prevalence, and its annual rate of malignant transformation is 1%, such that the actuarial probability of progression to a symptomatic monoclonal gammopathy at 25 years of follow-up is as high as 40%. The factors associated with a higher probability of malignant transformation are a relatively high plasma cell mass, immunoglobulin A M-protein type, and the "evolving" variant. It is recommended that patients with MGUS are monitored annually. Importantly, patients with asymptomatic monoclonal gammopathies must not be treated before the development of overt multiple myeloma.

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Prognostic Factors for Malignant Transformation in Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma

Abstract: Careful evaluation of marrow plasmacytosis, urinary paraprotein, background immunoglobulins, ESR, and paraprotein isotype might help identify at presentation patients with benign monoclonal gammopathies requiring stricter monitoring.

Cited by 165 publications

References 31 publications

Suppression of the noninvolved pair of the myeloma isotype correlates with poor survival in newly diagnosed and relapsed/refractory patients with myeloma

Suppression of the noninvolved pair of the myeloma isotype correlates with poor survival in newly diagnosed and relapsed/refractory patients with myeloma

Marcadores pronósticos en pacientes con gammapatía monoclonal de significado incierto

Smoldering multiple myeloma and monoclonal gammopathy of undetermined significance

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