Causes of death in patients with lymphoplasmacytic lymphoma.

e19079 Background: Lymphoplasmacytic lymphoma (LPL) is an indolent type of B-cell non-Hodgkin lymphoma. In the majority of cases, it presents as Waldenström Macroglobulinemia (WM), which is defined by the presence of bone marrow involvement and IgM monoclonal gammopathy. There are limited data regarding the causes of death in patients with LPL / WM. Methods: We conducted a retrospective review of 82 consecutive LPL patients followed in our Hematology/Oncology clinic between January 2000 and December 2025. Patients with IgM-MGUS were excluded from the analysis. Results: The median age at diagnosis was 72 years (range, 43-96), and 51 patients (62%) were male. The paraprotein was IgM-kappa, IgM-lambda, and other (IgA, biclonal IgM-kappa + IgM-lambda, or absent) in 55 (67%), 22 (27%), and 5 (6%) patients, respectively. Patients received a variety of chemotherapy and targeted agents, alone or in combination, with the most frequently administered being rituximab (n=36), corticosteroids (n=17), zanubrutinib (n=10), ibrutinib (n=8), bortezomib (n=7), bendamustine (n=6), chlorambucil (n=6), cyclophosphamide (n=6), carfilzomib (n=4), fludarabine (n=3), and others (n=7). Death occurred in 32 (39%) patients. The most common cause of death was infection (n=10), associated with chemotherapy in only 1 case. The second most frequent cause was metastatic cancer other than LPL: lung (n=4), prostate (n=3), squamous cell skin cancer (n=1), and acute myelogenous leukemia (n=1). Five patients died of comorbidities unrelated to LPL, and 2 patients died of traumatic causes. Only 5 (6%) patients died as a direct result of LPL, due to untreated hypercalcemia (n=2), thrombocytopenia (n=2), and anemia (n=1). Of note, the LPL of these 5 patients was intentionally left untreated, because of poor performance status due to advanced age and significant comorbidities, including dementia. Conclusions: In our experience of 82 consecutive LPL patients followed over 25 years, none died directly from LPL when able to receive appropriate therapy.