Extranodal Organ Involvement in Chronic Lymphocytic Leukemia: Clinical Features and Outcomes With Bruton Tyrosine Kinase and BCL ‐2 Inhibitors

ABSTRACT Background Although chronic lymphocytic leukemia (CLL) typically follows an indolent course involving blood, lymph nodes, and bone marrow, extranodal organ involvement is rare and poorly characterized. Methods We retrospectively analyzed 19 patients with histologically confirmed extranodal CLL or small lymphocytic lymphoma (SLL), assessing organ involvement, clinical features, genetic risk factors, and response to therapy. Results Different organs were affected, most frequently the kidneys (7/19). Median age at initial CLL diagnosis was 54 years, median time from CLL diagnosis to extranodal manifestation was 3 years. Genetic risk factors were comparable to typical CLL cohorts. Per treatment episode, exploratory overall response rate (ORR) for Bruton tyrosine kinase inhibitors (BTKi) was 88.9% (8/9); median progression‐free survival (PFS) from treatment initiation was 29 months. For venetoclax‐based regimens, ORR was 83.3% (5/6) and median PFS 52 months. Conclusions These data suggest meaningful activity of BTK and BCL‐2 inhibitors in CLL/SLL with extranodal organ involvement.