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. 2022 Apr 12;6(7):2230-2235.
doi: 10.1182/bloodadvances.2021004926.

Clonal hematopoiesis is associated with increased risk of progression of asymptomatic Waldenström macroglobulinemia

Sabrin Tahri  1   2   3   4   5 , Tarek H Mouhieddine  1   2   3   4   6 , Robert Redd  1   7 , Luisa Lampe  1   2   8 , Katarina I Nilsson  1   2   3   4 , Habib El-Khoury  1   2   3   4 , Nang Kham Su  1   2   3   4 , Amin H Nassar  1   9 , Elio Adib  9 , Govind Bindra  1 , Sarah Abou Alaiwi  1   9 , Lorenzo Trippa  1   10 , David P Steensma  1   2   4 , Jorge J Castillo  1   2   4   11 , Steven P Treon  1   2   11 , Irene M Ghobrial  1   2   3   4 , Adam S Sperling  1   2   3   4   12
Affiliations

Clonal hematopoiesis is associated with increased risk of progression of asymptomatic Waldenström macroglobulinemia

Sabrin Tahri et al. Blood Adv. .

Abstract

Clonal hematopoiesis (CH) is associated with adverse outcomes in patients with non-Hodgkin lymphoma (NHL) and multiple myeloma undergoing autologous stem cell transplantation. Still, its implications for patients with indolent NHL have not been well studied. We report the prevalence of CH in patients with Waldenström macroglobulinemia (WM) and its association with clinical outcomes. To unambiguously differentiate CH mutations from those in the WM clone, CH was defined by the presence of somatic mutations in DNMT3A, TET2, or ASXL1 (DTA) and was detected in 14% of 587 patients with IgM monoclonal gammopathy of undetermined significance (MGUS), smoldering WM (SWM) or WM. The presence and size of DTA clones were associated with older age. Patients with CH had an increased risk of progression from MGUS or SWM to WM, but not worse overall survival in this cohort. These findings further illuminate the clinical effects of CH in patients with indolent NHL such as WM.

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Figures

Figure 1.
Figure 1.
Mutational spectrum in patients with WM. (A) The total number of symptomatic patients with WM harboring ≥1 mutations in each gene. (B) The number of symptomatic patients with WM harboring mutations in 1, 2, and 3 different genes. (C) Co-mutation plot showing mutations present in all 258 patients: each column represents a single patient. The top row denotes the maximum VAF in each patient, with darker shades of pink indicating higher VAF. The bar graph on the right designates the proportion of the different mutation subtypes for each gene. OS (D) and PFS (E) among patients with WM with CH vs those without CH.
Figure 2.
Figure 2.
CH in patients with IgM MGUS and SWM. (A) Co-mutation plot showing mutations present in all 20 patients with IgM MGUS and patients with SWM: each column represents a single patient. The top row denotes the maximum VAF in each patient, with darker shades of pink indicating higher VAF. The bar graph on the right designates the proportion of the different mutation subtypes for each gene. PFS (B) and OS (C) among patients with IgM MGUS and those with SWM with CH vs those without CH. (D) Representative heat maps for the clonal dynamics of WM-related mutations and DTA mutations in WM. Values depicted in each square represent VAF. (E) Average change in VAF of DTA mutations assessed between consecutive time points, with or without intervening therapy.
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References

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