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 (p = 0.007). Additionally, patients receiving BTKi-based therapy at any point showed a trend toward improved survival (p = 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.