A single-center retrospective study suggests a potential benefit of BTK inhibitor-based therapy in patients with histologic transformation of Waldenström macroglobulinemia.

[BACKGROUND] Histologic transformation from Waldenström macroglobulinemia (WM) to diffuse large B-cell lymphoma (DLBCL) is a rare but clinically challenging event.

[METHODS] In this retrospective study, we analyzed 15 cases of histologic transformation among WM patients treated at the Department of Hematology, Jiangsu Province Hospital, between October 2015 and February 2025.

[RESULTS] The median age at transformation was 67 years, with a median time from initial WM diagnosis to transformation of 8 months (range: 0-177 months). Six patients (40%) received no WM-directed therapy before transformation. At transformation, 13 patients (86.7%) had stage IV disease. Extranodal involvement was frequent: 6 patients (40%) had ≥2 extranodal sites involved, with the most common sites being bone/bone marrow (each 33.3%), central nervous system (CNS, 20.0%), and nasopharynx/testis/gastrointestinal tract/peritoneum/skin (each 13.3%). Involvement of immune-privileged sites (CNS, testis) was observed in 5 patients (33.3%). Immunophenotyping revealed 13 cases (86.7%) as non-germinal center B-cell (non-GCB) DLBCL. Prognostic analysis showed a median overall survival (OS) of 26.0 months from transformation. Patients receiving Bruton's tyrosine kinase inhibitor (BTKi)-based regimens after transformation showed significantly prolonged OS ( = 0.007). Additionally, patients receiving BTKi-based therapy at any point showed a trend toward improved survival ( = 0.092).

[CONCLUSIONS] Although rare, histologic transformation from WM to DLBCL exhibits aggressive clinical behavior, frequent extranodal involvement, and poor prognosis. BTKi-based regimens may provide significant survival benefits in this patient population.