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SWOG 0120, A Prospective Observational Biologic Study of Asymptomatic Patients With Monoclonal Gammopathy and Plasma Proliferative Disorders

ABSTRACT: SWOG 0120, A Prospective Observational Biologic Study of Asymptomatic Patients With Monoclonal Gammopathy and Plasma Proliferative Disorders

PROVIDER: PRJNA504038 | ENA |

REPOSITORIES: ENA

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SWOG 0120, A Prospective Observational Biologic Study of Asymptomatic Patients With Monoclonal Gammopathy and Plasma Proliferative Disorders

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Defining an Ultra-Low Risk Group in Asymptomatic IgM Monoclonal Gammopathy.

Project description: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.

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Project description:Gene expression profiling of CD138 purified bone marrow plasma cells of previously untreated multiple myeloma patients and individual with monoclonal gammopathy of unknown significance (MGUS)

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Project description:The aim of this study was to identify the specific molecular biological features predicting the therapeutic outcomes of three bDMARDs, infliximab (IFX), tocilizumab (TCZ), and abatacept (ABT) by studying blood gene expression signature of patients prior to biologic treatment in a unified test platform. GSEA analyses showed that inflammasome genes were significantly upregulated in IFXâs NON-REM compared with its REM. In TCZâs REM, B cell-specifically expressed genes were upregulated. RNA elongation, apoptosis-related, and NK cell-specifically expressed genes were upregulated in ABTâs NON-REM. RA patients who responded inadequately to methotrexate and were later commenced with any one of IFX (n=140), TCZ (n=38), and ABT (n=31) as their first biologic between May 2007 and November 2011 were enrolled. Whole blood gene expression data were obtained prior to their biologic administration. They were defined as remission and non-remission groups, according to CDAI at 6 months of biologic therapy.

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Project description:Monoclonal gammopathy of undetermined significance (MGUS) is a benign condition with an approximate 1% annual risk of symptomatic plasma cell disorder development, mostly to multiple myeloma (MM). We performed genome-wide screening of copy-number alterations (CNAs) in 90 MGUS and 33 MM patients using high-density DNA microarrays. We identified CNAs in a smaller proportion of MGUS (65.6%) than in MM (100.0%, p=1.31×10-5) and showed median number of CNAs is lower in MGUS (3, range 0-22) than in MM (13, range 4-38, p=1.82×10-10). In the MGUS cohort, the most frequent losses were located at 1p (5.6%), 6q (6.7%), 13q (30.0%), 14q (14.4%), 16q (8.9%), 21q (5.6%) and gains at 1q (23.3%), 2p (6.7%), 6p (13.3%) and Xq (7.8%). Hyperdiploidy was detected in 38.9% of MGUS cases and the most frequent whole chromosome gains were 3 (25.6%), 5 (23.3%), 9 (37.8%), 15 (23.3%) and 19 (32.2%). We also identified CNAs such as 1p, 6q, 8p, 12p, 13q, 16q losses, 1q gain and hypodiploidy, which are potentially associated with an adverse prognosis in MGUS. In summary, we showed that MGUS is similar to MM in that it is a genetically heterogeneous disorder, but overall cytogenetic instability is lower than in MM, which confirms that genetic abnormalities play important role in monoclonal gammopathies.

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