Background: Non-IgM Lymphoplasmacytic Lymphoma (LPL) is a rare low-grade chronic lymphoproliferative disorder that constitutes less than 5% of all LPL cases. Clinical presentation and bone marrow pathological findings are usually similar to other LPL cases.

Case Report: This is a case report of a 90-year-old male, who initially presented with severe anemia secondary to bleeding from a fall. Patient was also found to have leukopenia and thrombocytopenia. Further workup established a diagnosis of lymphoplasmacytic lymphoma with IgA monoclonal gammopathy. Patient started treatment with a Bruton-kinase inhibitor, Zanubrutinib in December 2024 to which he initially showed a drop in the IgA monoclonal protein, suggesting a positive response. About three months after staring the treatment, patient developed complications with Influenza A and new onset atrial fibrillation with rapid ventricular response. His general condition gradually deteriorated and subsequently passed away.

Conclusion: Non-IgM LPL cases constitute a small number of LPL cases with similar presentation and are either non-secretory or associated with IgG or IgA monoclonal proteins. Serum immunofixation usually confirms the type of monoclonal gammopathy. Although the treatments are generally similar, prognosis of non-IgM LPL is worse than IGM LPL.

Keywords: Non-IgM Lymphoplasmacytic Lymphoma (LPL); Zanubrutinib; MYD88 mutation; CXCR4 mutation