Impact of MYD88L265P mutation status on histological transformation of Waldenström Macroglobulinemia

Abstract

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 12/31/2017 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=0.003]. Additionally, the MYD88^WT status was independently associated with shorter time‐to‐transformation [HR 7.9 (95%CI: 2.3‐27; p=0.001)], with a 5‐year transformation rate of 16% for MYD88^WT versus 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; pMYD88^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.