Concurrent profound response of both Waldenström’s macroglobulinemia and myeloproliferative neoplasm to zanubrutinib

Introduction: Waldenström’s macroglobulinemia (WM), characterized by the presence of indolent B-cell lymphoplasmacytic lymphoma with immunoglobulin M (IgM) overproduction and MYD88 or CXCR4 mutations, is extremely rarely associated with myeloproliferative neoplasms (MPNs). Bruton’s tyrosine kinase inhibitors (BTKis) are effective in WM, but their effect in MPNs is poorly understood. Material and methods: We present the case of a 61-year-old man who simultaneously had WM with a high IgM concentration (25.12 g/L) and high-risk myeloproliferative neoplasm not otherwise specified (MPN-NOS) associated with thrombocythemia, reticulin fibrosis 2+ in the bone marrow, and a JAK2 mutation. WM was treated with the BTKi zanubrutinib as monotherapy, while hydroxycarbamide was administered for cytoreduction of MPN. Treatment outcomes were assessed after 6 months of therapy with zanubrutinib. Results: A profound response of WM was achieved, including complete normalization of IgM concentration and disappearance of the MYD88 L265P mutation [very good partial response (VGPR) according to the International Workshop for Waldenström’s Macroglobulinemia (IWWM)], as well as simultaneous regression of myeloproliferative parameters: a decrease in platelet count (from 789 × 10 9 /L to < 500 × 10 9 /L), enabling complete discontinuation of hydroxycarbamide; a reduction in the degree of bone marrow reticulin fibrosis from 2+ to 1+; and maintenance of the JAK2 V617F mutation frequency at 18% variant allele frequency (VAF), without further increase. No significant adverse events were observed. Conclusions: Zanubrutinib induced a simultaneous, profound response in both the cellular component of WM and MPN parameters, demonstrating the importance of BTK inhibition in the treatment of concomitant lymphoproliferative and myeloproliferative neoplasms. This case warrants further investigation into the role of zanubrutinib in MPN.