Impact of MYD88^L265P mutation status on histological transformation of Waldenström Macroglobulinemia

Histological transformation in Waldenström macroglobulinemia (WM) is an uncommon complication, with limited data, particularly regarding the impact of MYD88^L265P mutation on transformation. We examined risk factors and outcomes associated with transformation in WM, highlighting the role of MYD88^L265P mutation. Patients with WM seen at Mayo Clinic, Rochester, USA and University Hospital of Reims, France, between 01/01/1996 and December 31, 2017 were included; 50 (4.3%) of 1147 patients transformed to a high-grade lymphoma, with median time-to-transformation of 4.5 (range 0-21) years in the transformed cohort. The MYD88^L265P mutation status was known in 435/1147 (38%) patients (406 with non-transformed WM and 29 patients in transformed cohort). On multivariate analysis, MYD88^WT status alone was an independent predictor of transformation (odds ratio, 7[95%CI: 2.1-23]; P =.003). Additionally, the MYD88^WT status was independently associated with shorter time-to-transformation (HR 7.9 [95%CI: 2.3-27; P =.001]), with a 5-year transformation rate of 16% for MYD88^WT vs 2.8% with MYD88^L265P mutated patients. Patients with transformation demonstrated a significant increase in risk of death compared to patients who did not transform (HR 5.075; 95%CI: 3.8-6.8; P <.001). In conclusion, the MYD88^WT status is an independent predictor of transformation and associated with a shorter time-to-transformation. Additionally, transformation conferred an inferior overall survival in patients with WM.