Rapid response to obinutuzumab and venetoclax in patients with nephrotic syndrome related to CLL: a report of two cases

Nephrotic syndrome caused by membranoproliferative glomerulonephritis (MPGN) related to chronic lymphocytic leukemia (CLL) is a rare condition. Due to the rarity, no standard of care has been established yet. The combination of rituximab, chlorambucil and fludarabin was described as an effective therapeutic regimen. However, the efficacy of the novel therapeutic options in CLL-induced nephrotic syndrome are rarely reported so far. We report two cases of patients with CLL suffering from concomitant nephrotic syndrome with significant proteinuria. The patients have consented to the evaluation and publication of their data. The patients received their initial diagnosis at our clinic and were followed for approximately 3 years. The first patient, a 44-year old female with B-CLL, Binet A, and a low risk CLL-IPI score. Initially lupus nephritis was suspected to be associated with MPGN. However, despite the immunosuppressive treatment with mycophenolate mofetil and prednisolone no disease control was achieved. Consequently, CLL-associated nephrotic syndrome was assumed, and treatment with obinutuzumab and venetoclax was initiated. Six weeks after therapy initiation, the patient showed complete clinical resolution of nephrotic syndrome, accompanied by a marked reduction in proteinuria. The second patient, a 73-year old man, diagnosed with B-CLL, Binet C, CLL-IPI score intermediate risk presenting with concomitant MPGN. Treatment with obinutuzumab and venetoclax was initiated. Clinically, the nephrotic syndrome resolved within a few weeks after the initiation of therapy. Final assessment after completion of treatment by computed tomography and flow cytometry demonstrated complete remission of CLL. In addition, proteinuria completely resolved. At the last follow-up, the patient remains in sustained remission, with proteinuria persistently below the nephrotic range. In this report, we present two cases of CLL-related nephrotic syndromes, successfully treated with obinutuzumab and venetoclax. Furthermore, we emphasize the importance of awareness of this rare complication in patients with CLL.