Disease outcomes and biomarkers of progression in smouldering Waldenström macroglobulinaemia
Saurabh Zanwar, Jithma P. Abeykoon, Stephen M. Ansell, Morie A. Gertz, Colin Colby, Dirk R. Larson, Jonas Paludo, Rong He, Rahma Warsame, Patricia T. Greipp, Rebecca L. King, Carrie A. Thompson, Thomas E. Witzig, Martha Q. Lacy, Wilson I. Gonsalves, Grzegorz S. Nowakowski, David Dingli, Ronald S. Go, Thomas M. Habermann, S. Vincent Rajkumar, Robert A. Kyle, Shaji Kumar, Prashant Kapoor
Abstract
Summary 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 β 2 ‐microglobulin (β 2 M) ≥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 ( MYD88 WT ) 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 MYD88 L265P 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 CXCR4 WT vs. 5·6 years for CXCR4 MUT , 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 β 2 M 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.