Tailored Management of Chronic Lymphocytic Leukemia-Related Monoclonal Gammopathy of Renal Significance in an Elderly Patient with Severe Kidney Impairment

Introduction: Effective management of chronic lymphocytic leukemia-related monoclonal gammopathy of renal significance (CLL-MGRS) requires a nuanced approach. Balancing efficacy, tolerability, and timing is key to achieving a durable response and ensuring safety. We report the successful management of an elderly patient with CLL-MGRS, highlighting strategies to mitigate the risk of treatment-related toxicities. Case Description: An 82-year-old Chinese man presented with nephritic-nephrotic syndrome (>585 urinary RBC/UL; uPCR 7.36g/g; sAlb 28G/L), hypocomplementemia, and progressive chronic kidney disease (peak sCr 388µmol/L), occurring on a background of untreated CLL (lymphocyte count of 77x109/L). Kidney biopsy revealed IgG1/λ proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID), lymphocytic infiltration (30-40%), and moderate tubular atrophy/interstitial fibrosis. He was assessed to have a narrow window for intervention, with a high risk of tumor lysis syndrome (TLS). Pre-phase prednisolone and rituximab (375mg/m2 over 2 days) was started to reduce tumor burden prior to initiating venetoclax and obinutuzumab (VEN+OBI) therapy. TLS prophylaxis with allopurinol and judicious hydration was instituted. A pre-emptive central venous catheter was inserted in anticipation of potential dialysis. After 1 cycle of OBI+VEN, VEN was withheld due to grade 3 cytopenias. OBI monotherapy was continued with G-CSF support. Partial renal recovery was observed at 6 months (sCr 197µmol/L; sAlb 39G/L; uPCR 0.31g/g). Discussion: Integrated hematology and nephrology expertise is essential in managing MGRS, where both hematologic response and renal preservation are critical. Ongoing hemato-nephrology collaboration allows dynamic treatment adjustment to achieve these goals. An ideal treatment should deliver rapid, deep, and durable clonal suppression to reverse kidney injury. In CLL, BTK inhibitors have improved tolerability, yet their slower onset of action limits their utility in scenarios needing urgent disease control. VEN+OBI offered rapid disease control but required intensive TLS prophylaxis and close monitoring. Toxicities in this patient were managed with timely modifications, enabling continued therapy and clinical benefit. This case highlights the feasibility of effective, individualised treatment in a high-risk population.