CXCR4 mutations affect presentation and outcomes in patients with Waldenström macroglobulinemia: A systematic review

Abstract

Introduction: The genomic landscape of Waldenström macroglobulinemia (WM) is characterized by recurrent MYD88 (MYD88^L265P) and CXCR4 mutations (CXCR4^MUT), detected in 90% and 30% of cases, respectively. The role of CXCR4^MUT in clinical features and outcomes to therapy in WM patients is evolving. Areas covered: We performed a systematic review aimed at evaluating the prevalence of CXCR4^MUT in WM patients, and at assessing differences in clinical features and outcomes to therapy between WM patients with and without CXCR4^MUT. Seventeen studies were included in our analysis. The pooled prevalence of CXCR4^MUT in WM patients was 31%; 34% in MYD88^L265P and 5% in MYD88^WT patients. CXCR4^MUT were associated with higher serum IgM levels and higher risk of hyperviscosity than CXCR4^WT patients. Very good partial response (VGPR) and progression-free survival (PFS) rates to ibrutinib, with and without rituximab, appeared lower in CXCR4^MUT than in CXCR4^WT patients. Response and PFS rates were not affected by CXCR4^MUT status on patients treated with proteasome inhibitors. Expert opinion: Our systematic review shows that WM patients with CXCR4^MUT have specific clinical features and have lower response and PFS rates to BTK inhibitors. Our findings support standardization of CXCR4 testing and development of CXCR4-directed therapy.

Keywords: Waldenstrom macroglobulinemia; cxcr4; ibrutinib; outcomes; rituximab.