TP53 mutations are associated with mutated MYD88 and CXCR4, and confer an adverse outcome in Waldenström macroglobulinaemia

Summary Little is known about TP53 mutations in Waldenström Macroglobulinaemia (WM). We evaluated 265 WM patients for TP53 mutations by next‐generation sequencing, and validated the findings by Sanger sequencing. TP53 mutations were identified and validated in 6 (2·6%) patients that impacted the DNA‐binding domain. All six were MYD88‐ and CXCR4‐mutated. Ibrutinib showed activity in patients carrying all three mutations. With a median follow‐up of 18 months, 2 (33%) with biallelic TP53 inactivation died of progressive disease. TP53 mutations are rare in WM, and associate with MYD88 and CXCR4 mutations. WM patients with TP53 mutations show response to ibrutinib.