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- Title
Defining an Ultra-Low Risk Group in Asymptomatic IgM Monoclonal Gammopathy.
- Authors
Moreno, David F.; Pereira, Arturo; Tovar, Natalia; Cibeira, María Teresa; Magnano, Laura; Rozman, María; López-Guerra, Mónica; Colomer, Dolors; Martín-Antonio, Beatriz; Jiménez-Segura, Raquel; Isola, Ignacio; Rodríguez-Lobato, Luis Gerardo; Oliver-Caldés, Aina; Mena, Mari Pau; Rosiñol, Laura; Bladé, Joan; Fernández de Larrea, Carlos; Roccaro, Aldo M.
- Abstract
Simple Summary: Patients with asymptomatic IgM monoclonal gammopathies include IgM monoclonal gammopathy of undetermined significance (IgM MGUS) and smoldering Waldenström macroglobulinemia (SWM), all with some risk of progression to symptomatic Waldenström macroglobulinemia, amyloidosis, or other lymphoproliferative disorder. Due to their low incidence, few studies have focused on the risk of progression, with SWM being the most studied. As both are recognized clinical-pathological entities that share similar clonal and phenotypical features, we focus on defining new biomarkers of progression in this population with long follow-up. We analyzed 171 patients with asymptomatic IgM monoclonal gammopathies (64 with IgM monoclonal gammopathy of undetermined significance—MGUS and 107 with smoldering Waldenström macroglobulinemia - SWM) who had a bone marrow (BM) evaluation performed at diagnosis. Abnormal free-light chain ratio (53% vs. 31%) and MYD88 mutation prevalence (66% vs. 30%) were higher in patients with SWM. No other differences were found among groups. With a median follow-up of 4.3 years, 14 patients progressed to Waldenström macroglobulinemia, 1 to amyloidosis, and 28 died without progression. The MYD88 mutation was found in 53% of patients (available in 160 patients). Multivariate analysis showed that immunoparesis (subhazard ratio—SHR 10.2, 95% confidence interval—CI: 4.2–24.8; p < 0.001) and BM lymphoplasmacytic infiltration ≥ 20% (SHR: 6, 95% CI: 1.6–22.1; p = 0.007) were associated with higher risk of progression. We developed a risk model based on these two risk factors. In the absence of both variables, an ultra-low risk group was identified (SHR 0.1, 95% CI 0.02–0.5; p = 0.004), with 3% and 6% of cumulative incidence of progression at 10 and 20 years, respectively. Bootstrap analysis confirmed the reproducibility of these results. This study finds immunoparesis and BM infiltration as biomarkers of progression as well as a low-risk group of progression in asymptomatic IgM monoclonal gammopathies.
- Subjects
DISEASE progression; IMMUNOGLOBULINS; PARAPROTEINEMIA; ACQUISITION of data methodology; GENETIC mutation; AMYLOIDOSIS; CONFIDENCE intervals; MULTIVARIATE analysis; MONOCLONAL gammopathies; RISK assessment; CANCER patients; COMPARATIVE studies; MEDICAL records; DISEASE prevalence; DESCRIPTIVE statistics; LYMPHOPROLIFERATIVE disorders; TUMOR markers; BONE marrow; PREDICTION models; LONGITUDINAL method; DISEASE risk factors; SYMPTOMS
- Publication
Cancers, 2021, Vol 13, Issue 9, p2055
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers13092055