IntroductionMinimal residual disease (MRD) has been recognized as an important prognostic factor of survival in patients with hematological malignancies. However, the prognostic value of MRD in Waldenström macroglobulinemia (WM) remains unexplored.MethodsWe analyzed 108 newly diagnosed WM patients receiving systematic therapy and assessed for MRD by multiparameter flow cytometry (MFC) using bone marrow samples.ResultsOf the total patients, 34 (31.5%) achieved undetectable MRD (uMRD). A hemoglobin level of >115 g/L (P=0.03), a serum albumin level of >35 g/L (P=0.01), a β2-MG level of ≤3 mg/L (P=0.03), and a low-risk International Prognostic Scoring System for WM (IPSSWM) stage (P<0.01) were associated with a higher rate of uMRD. Improvements in monoclonal immunoglobulin (P<0.01) and hemoglobin (P=0.03) levels were more evident in uMRD patients compared with that in MRD-positive patients. The 3-year progression-free survival (PFS) was better in uMRD patients compared with that in MRD-positive patients (96.2% vs. 52.8%; P=0.0012). Landmark analysis also showed that uMRD patients had better PFS compared with MRD-positive patients after 6 and 12 months. Patients who achieved partial response (PR) and uMRD had a 3-year PFS of 100%, which was significantly higher than that of patients with MRD-positive PR (62.6%, P=0.029). Multivariate analysis showed that MRD positivity was an independent factor of PFS (HR: 2.55, P=0.03). Moreover, the combination of the 6th International Workshop on WM assessment (IWWM-6 Criteria) and MRD assessment had a higher 3-year AUC compared with the IWWM-6 criteria alone (0.71 vs. 0.67).DiscussionMRD status assessed by MFC is an independent prognostic factor for PFS in patients with WM, and its determination could improve the precision of response evaluation, especially in patients who achieved PR.