Clinical characteristics and outcome of CLL/SLL patients with renal involvement in the era of targeted drugs
Ling Gao, Minjie Yu, Lixia Sheng, Zhen Wang, Bo Zhang, Xiaoqian Liu, Tonglu Qiu, Wei Zhang, Luomengjia Dai, Ziyuan Zhou, Lei Fan, Jianyong Li, Huayuan ZhuBackground
Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) is a clonal mature B-cell neoplasm with rare extranodal organ renal involvement.
Objectives
To summarize the clinical and pathological characteristics of biopsy-confirmed CLL/SLL-associated renal lesions and evaluate the efficacy of targeted combination therapy.
Design
Retrospective multicenter observational study.
Methods
Eleven patients with CLL/SLL-associated nephropathy were enrolled from January 2017 to October 2024 across three Chinese centers. As of December 31, 2025, data were collected through electronic medical records and telephone follow-up.
Results
The median age was 58 (range 40–72) years. Among tested patients, 88.9% (8/9) exhibited IGHV mutation and 62.5% (5/8) were CLL-IPI low-risk, and no TP53 mutations were detected. The median time from CLL diagnosis to renal biopsy was 40.7 months (range: 0.2–58 months). Biopsy indictions included proteinuria (90.9%, 10/11), hematuria (54.5%, 6/11), renal dysfunction (54.5%, 6/11), and nephrotic syndrome (9.1%, 1/11). Main pathologies were tumor cell interstitial infiltration (45.5%, 5/11), membranoproliferative glomerulonephritis (27.3%, 3/11), membranous nephropathy (18.2%, 2/11), and C3 glomerulonephritis (9.1%, 1/11). Concomitant monoclonal gammopathy and cryoglobulinemia were observed in 27.3% and 18.2%, respectively. Nine patients received BTKi -based therapy. The best overall response rate (ORR) for CLL/SLL was 100%, with a CR rate of 72.7%. According to KDIGO 2021 guidelines, the renal best ORR was 100%, with a CR rate of 36.4%. Four patients achieved CR in both CLL and renal assessments. As of December 31, 2025, the median follow-up was 70.1 months and median PFS was not reached. Grade ≥3 hematologic toxicities included neutropenia (27.3%) and thrombocytopenia (18.2%). Common non-hematologic adverse events were COVID-19 (27.3%), bleeding (18.2%), and gastrointestinal symptoms (18.2%), all of grade 1-2.
Conclusions
CLL/SLL with renal involvement is associated with a favorable IGHV-mutated profile. Interstitial infiltration and membranoproliferative glomerulonephritis are the predominant renal pathologies. BTKi-based regimens were associated with favorable hematologic and renal outcomes in this small cohort.