Liquid biopsy-directed therapy in primary bone lymphoma: venetoclax-Pola-R-CHP and CAR-T achieve molecular remission:...

Primary bone lymphoma (PBL) is a rare extranodal subtype of diffuse large B-cell lymphoma (DLBCL) that poses significant diagnostic challenges due to nonspecific clinical and radiological features. Molecular profiling and ctDNA monitoring now offer promising approaches for precision treatment and disease surveillance in DLBCL.

A 54-year-old woman presented with persistent knee pain and multiple osteolytic lesions. After several nondiagnostic biopsies, open surgical biopsy confirmed germinal center B-cell-like DLBCL with high-risk molecular features (BCL2/MYC rearrangements, EZB subtype). The patient received molecularly guided therapy with Pola-R-CHP plus venetoclax, achieving complete metabolic remission. However, persistent MEF2B and TET2 mutations in ctDNA indicated MRD positivity, prompting consolidative CAR-T therapy (axicabtagene ciloleucel), after which she achieved sustained molecular remission with undetectable ctDNA.

This case highlights three key aspects in managing PBL: the critical role of surgical biopsy for definitive diagnosis, particularly with concealed lesions; the value of molecular profiling in guiding targeted therapy; and the utility of ctDNA monitoring for MRD detection and treatment guidance. An integrated approach incorporating these strategies may improve outcomes for this rare lymphoma subtype.