MGUS and clonal hematopoiesis show unrelated clinical and biological trajectories in an older population cohort

Matteo Claudio Da Vià, Marta Lionetti, Alessio Marella, Antonio Matera, Erica Travaglino, Elena Signaroldi, Alessia Antonella Galbussera, Ugo Lucca, Sara Mandelli, Emma Riva, Mauro Tettamanti, Loredana Pettine, Alessandra Pompa, Luca Baldini, Antonino Neri, Matteo Giovanni Della Porta, Niccolò Bolli, Matteo Claudio Da Vià, Marta Lionetti, Alessio Marella, Antonio Matera, Erica Travaglino, Elena Signaroldi, Alessia Antonella Galbussera, Ugo Lucca, Sara Mandelli, Emma Riva, Mauro Tettamanti, Loredana Pettine, Alessandra Pompa, Luca Baldini, Antonino Neri, Matteo Giovanni Della Porta, Niccolò Bolli

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) and clonal hematopoiesis (CH) are 2 preclinical clonal expansions of hematopoietic cells whose prevalence rises with age, reaching almost 10% in people of aged 70 years and older. The increased risk of myeloid malignancies in patients with myeloma is well defined, and the study of the association between CH and MGUS could help explain this phenomenon. Here, we analyzed a fully clinically annotated dataset of 777 older subjects (median age, 91 years) previously screened for prevalence of CH. The prevalence of MGUS and CH was 9.6% and 17.3%, respectively. We detected CH in 9.7% of the patients with MGUS and MGUS in 5.5% of the patients with CH. We did not find a significant correlation between the presence of MGUS and CH. Furthermore, the 2 conditions showed a differential association with clinical and laboratory covariates, suggesting that MGUS and CH may represent age-associated unrelated clonal drifts of hematopoietic cells. Confirmatory studies are needed to assess the relevance of CH in plasma cell disorders. This trial was registered at www.clinicaltrials.gov as #NCT03907553.

Conflict of interest statement

Conflict-of-interest disclosure: N.B. received honoraria from Celgene, Amgen and Janssen. The other authors declare no competing financial interests.

© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Figures

Figure 1.
Figure 1.
Forest plots of multivariate analyses to determine the possible association between MGUS and CH. (A) Forest plot using CH as independent variable. (B) Forest plot using MGUS as independent variable. CI, confidence interval; OR, odds ratio.

References

    1. Kyle RA. Monoclonal gammopathy of undetermined significance. Natural history in 241 cases. Am J Med. 1978;64(5):814–826.
    1. Oben B, Froyen G, Maclachlan KH, et al. Whole-genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities. Nat Commun. 2021;12(1):1861.
    1. Yoshida K, Gowers KHC, Lee-Six H, et al. Tobacco smoking and somatic mutations in human bronchial epithelium. Nature. 2020;578(7794):266–272.
    1. Steensma DP, Bejar R, Jaiswal S, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9–16.
    1. Genovese G, Kähler AK, Handsaker RE, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014;371(26):2477–2487.
    1. Jaiswal S, Fontanillas P, Flannick J, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371(26):2488–2498.
    1. Zink F, Stacey SN, Norddahl GL, et al. Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. Blood. 2017;130(6):742–752.
    1. McKerrell T, Park N, Moreno T, et al. Understanding Society Scientific Group Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis. Cell Rep. 2015;10(8):1239–1245.
    1. Landgren O, Hofmann JN, McShane CM, et al. Association of immune marker changes with progression of monoclonal gammopathy of undetermined significance to multiple myeloma. JAMA Oncol. 2019;5(9):1293–1301.
    1. Landgren O, Kyle RA, Pfeiffer RM, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: A prospective study. Blood. 2009;113(22):5412–5417.
    1. Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354(13):1362–1369.
    1. Mouhieddine TH, Sperling AS, Redd R, et al. Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant. Nat Commun. 2020;11(1):2996.
    1. Mailankody S, Pfeiffer RM, Kristinsson SY, et al. Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS) Blood. 2011;118(15):4086–4092.
    1. Berthon C, Nudel M, Boyle EM, et al. Acute myeloid leukemia synchronous with multiple myeloma successfully treated by azacytidine/lenalidomide and daratumumab without a decrease in myeloid clone size. Leuk Res Rep. 2020;13
    1. Niroula A, Sekar A, Murakami MA, et al. Distinction of lymphoid and myeloid clonal hematopoiesis. Nat Med. 2021;27(11):1921–1927.
    1. Lucca U, Tettamanti M, Logroscino G, et al. Prevalence of dementia in the oldest old: the Monzino 80-plus population based study. Alzheimers Dement. 2015;11(3):258–270.e3.
    1. Rossi M, Meggendorfer M, Zampini M, et al. Clinical relevance of clonal hematopoiesis in persons aged ≥80 years. Blood. 2021;138(21):2093–2105.
    1. Hecker JS, Hartmann L, Rivière J, et al. CHIP and hips: clonal hematopoiesis is common in patients undergoing hip arthroplasty and is associated with autoimmune disease. Blood. 2021;138(18):1727–1732.
    1. Holstein SA, Jung SH, Richardson PG, et al. Updated analysis of CALGB (Alliance) 100104 assessing lenalidomide versus placebo maintenance after single autologous stem-cell transplantation for multiple myeloma: A randomised, double-blind, phase 3 trial. Lancet Haematol. 2017;4(9):e431–e442.
    1. Attal M, Lauwers-Cances V, Marit G, et al. IFM Investigators Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366(19):1782–1791.
    1. McCarthy PL, Holstein SA, Petrucci MT, et al. Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: A meta-analysis. J Clin Oncol. 2017;35(29):3279–3289.
    1. Tahri S, Mouhieddine TH, Redd R, et al. Clonal hematopoiesis is associated with increased risk of progression of asymptomatic Waldenström macroglobulinemia. Blood Adv. 2022;6(7):2230–2235.
    1. Klimkowska M, Nannya Y, Gran C, et al. Absence of a common founder mutation in patients with cooccurring myelodysplastic syndrome and plasma cell disorder. Blood. 2021;137(9):1260–1263.

Source: PubMed

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