Disease outcomes and biomarkers of progression in smouldering Waldenström macroglobulinaemia

Saurabh Zanwar, Jithma P. Abeykoon, Stephen M. Ansell, Morie A. Gertz, Colin Colby, Dirk Larson, Jonas Paludo, Rong He, Rahma Warsame, Patricia T. Greipp, Rebecca L. King, Carrie A. Thompson, Thomas E. Witzig, Martha Q. Lacy, Wilson Gonsalves, Grzegorz S. Nowakowski, David Dingli, Ronald S. Go, Thomas M. Habermann, S. Vincent RajkumarRobert A. Kyle, Shaji Kumar, Prashant Kapoor

Research output: Contribution to journalArticlepeer-review


Patients with asymptomatic/smouldering Waldenström macroglobulinaemia (SWM) have a variable risk of progression to active WM. Our study evaluated 143 patients with SWM consecutively seen between January 1996 and December 2013. With a median [95% confidence interval (CI)] follow-up of 9·5 [8·1–11·5] years, the cumulative rate of progression was 11% at 1 year, 38% at 3 years and 55% at 5 years. On multivariate analysis, haemoglobin (Hb) ≤123 g/l [risk ratio (RR) 2·08; P = 0·009] and β2-microglobulin (β2M) ≥2·7 µg/ml (RR 2·0; P = 0·01) were independent predictors of a shorter time-to-progression (TTP) to active WM. Patients with myeloid differentiation factor 88 wild type (MYD88WT) genotype (n = 11) demonstrated a trend toward shorter TTP [median (95% CI) 1·7 (0·7–8·7) vs. 4·7 (2·4–7·7) years for the MYD88L265P cohort, n = 42; P = 0·11]. The presence of C-X-C chemokine receptor type 4 (CXCR4) mutation (n = 29) did not impact the TTP (median: 3 years for CXCR4WT vs. 5·6 years for CXCR4MUT, P = 0·34). The overall survival (OS) for patients with SWM (median: 18·1 years) was comparable to an age-, sex- and calendar year-matched USA population (median: 20·3 years, P = 0·502). In conclusion, Hb and β2M at diagnosis represent independent predictors of progression to active WM. Comparable survival of SWM and a matched USA population argues against pre-emptive intervention in this patient population.

Original languageEnglish (US)
Pages (from-to)210-216
Number of pages7
JournalBritish journal of haematology
Issue number2
StatePublished - Oct 2021


  • CXCR4
  • IgM monoclonal gammopathy
  • MYD88
  • asymptomatic lymphoplasmacytic lymphoma

ASJC Scopus subject areas

  • Hematology


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