Secondary Acute Myeloid Leukemia with Shared TP53 Mutation Following Zanubrutinib-Rituximab for High-Risk Mantle Cell Lymphoma: Clonal Evolution or Treatment Effect?
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Secondary myeloid neoplasms have been reported with ibrutinib and acalabrutinib but not with zanubrutinib. We present a female patient in her late 80s with TP53-deleted pleomorphic mantle cell lymphoma who achieved metabolic complete remission with zanubrutinib-rituximab but remained MRD-positive for TP53. Eighteen months later, she developed AML harboring TP53, NPM1, FLT3-TKD, and DNMT3A mutations. The shared TP53 mutation and persistent MRD suggest clonal evolution from a common hematopoietic progenitor rather than drug-induced leukemogenesis, though zanubrutinib's potential role in facilitating this evolution through immunosuppression and clonal selection cannot be excluded.
