Disease outcomes and biomarkers of progression in smouldering Waldenström macroglobulinaemia.

Abstract

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 1year, 38% at 3years and 55% at 5years. On multivariate analysis, haemoglobin (Hb) ≤123g/l [risk ratio (RR) 2·08; P=0·009] and β2 -microglobulin (β2 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 (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: 3years for CXCR4WT vs. 5·6years for CXCR4MUT , P=0·34). The overall survival (OS) for patients with SWM (median: 18·1years) was comparable to an age-, sex- and calendar year-matched USA population (median: 20·3years, P=0·502). In conclusion, Hb and β2 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.