Phospholipase A2 receptor antibody mediated membranous nephropathy associated with cemiplimab

Abstract

Background: Immune checkpoint inhibitors (ICI) are a fast growing therapy used in several types of malignancies. The majority of immune related adverse events observed in the kidney are due to acute interstitial nephritis. Glomerular diseases although less common have also been described. Case Presentation: We present a case of phospholipase A2 receptor positive membranous nephropathy triggered by ICI therapy cemiplimab (PD1 inhibitor) in a 88 year old man with no prior history of proteinuria or glomerular disease. The patient responded to steroid monotherapy with rapid clinical and immunological remission. Conclusion: While patients undergoing ICI therapy warrant close monitoring of systemic immune related adverse events, physicians should remain vigilant of kidney related events and obtain a kidney biopsy if clinically indicated.

Membranous Nephropathy After Exposure to Immune Checkpoint Inhibitors

“…We conducted a literature search of published cases of MN occurring after ICI exposure and identified 11 additional reports, 4 , 5 , 6 , 7 , 8 , 9 , S1–S4 leading to a series of 13 patients who are summarized in Table 1 .…”

“…S10 As depicted in Table 1 , most patients developed anti-PLA2R antibodies, detected either in serum or kidney biopsy specimen. Screening was positive for 6 out of 10 patients tested for the anti-PLA2R autoantibody, 8 , 9 , S2 , S3 1 patient for the anti- thrombospondin type-I domain-containing 7A autoantibody, S1 and 1 patient for the anti- neural epidermal growth factor-like 1 autoantibody. S4 It is known that ICIs induce B-cell subset changes that correlate with increased circulating antibodies directed both against self and cancer antigens.…”

Case report: Anti-PLA2R positive membranous nephropathy associated with atezolizumab

“…Withholding of cemiplimab and treatment with oral corticosteroids achieved remission. 8 Because ICIs represent a new strategy for survival in cancer patients, their use is becoming widespread leading to a potential epidemic of irAEs. Acute kidney injury in the setting of AIN is the most frequent renal irAEs, consequently, the ASCO renal toxicity guidelines recommend monitoring serum creatinine before every dose.…”

Onconephrology 2022: An Update

“…Since then, several other glomerular pathologies have been reported and observed (unpublished) in clinical practice such as MN, mesangioproliferative glomerulonephritis and other podocytopathies. [80][81][82][83] (Figure 3).…”

“…80 Since then, several other glomerular pathologies have been reported and observed (unpublished) in clinical practice such as MN, mesangioproliferative GN, and other podocytopathies (Figure 3). [80][81][82][83] Treatment of glomerular diseases associated with ICI is challenging.…”