Case Report: Rapid renal response to venetoclax monotherapy in a CLL patient with secondary membranous glomerulonephritis

Abstract

Membranous glomerulonephritis (MGN) is a rare extra-hematological autoimmune complication of chronic lymphocytic leukemia (CLL), clinically characterized by nephrotic-range proteinuria and, less frequently, renal failure. Because of the rarity of this condition, there is no standardized treatment. Chlorambucil and fludarabine-based regimens, possibly combined with rituximab, have been historically the most frequent therapeutic approaches, with renal response obtained in about two-third of the patients. However, responses are often transient and partial. Here we describe the first patient with rituximab-refractory, CLL-related MGN successfully treated with the Bcl-2 antagonist venetoclax. Nephrotic syndrome resolved as soon as three months after venetoclax initiation, with no unexpected toxicities. At the last follow-up, 17 months after venetoclax start, renal response persists, with proteinuria below 0.5 g/24 hours. This case suggests that targeted agents, particularly Bcl-2 antagonists, might be suitable options for patients with renal autoimmune disorders arising in the context of CLL.

How to Choose the Right Treatment for Membranous Nephropathy

“…In addition, secondary MN of Castleman's disease has been successfully treated with tocilizumab from both a renal and hematological perspective [105,106]. Another cause of MN is represented by chronic lymphocytic leukemia; such cases have been treated with RTX over the years and, more recently, venetoclax has been successfully used in a refractory patient [107]. Membranous lupus nephritis accounts for almost 15% of lupus nephritis (LN).…”