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Kidney Week

Abstract: PO2192

Immune Checkpoint Inhibitor-Associated Reactivation of Primary Membranous Nephropathy Responsive to Rituximab

Session Information

  • Onco-Nephrology - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Onco-Nephrology

  • 1500 Onco-Nephrology

Authors

  • Lin, Jamie, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Wang, Daniel Y., Baylor College of Medicine, Houston, Texas, United States
  • Mamlouk, Omar, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Glass, William F., University of Texas Health Science Center at Houston, Houston, Texas, United States
  • Abudayyeh, Ala, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Introduction

The same mechanisms that mediate immune checkpoint inhibitor (ICI) anti-tumor efficacy also increases the activity of the immune system and can lead to immune-related adverse events (irAEs). Those with preexisting autoimmune disease are particularly vulnerable. We report the first case of ICI associated reactivation of primary membranous nephropathy (MN) responsive to rituximab in a patient with mesothelioma and successful continued ICI treatment.

Case Description

A 60-year-old male with primary MN was diagnosed with stage IA malignant pleural mesothelioma (MPM) in September 2018. Shortly after receiving nivolumab his proteinuria began to increase and his nephrologist recommended conservative management. In November 2019, the patient came to nephrology clinic at MD Anderson Cancer Center for a second opinion. Notable labs included: albumin 1.9 g/dl, creatinine (Cr) 1.25 mg/dl (baseline Cr 0.82-0.91 mg/dl), and a 24-hour urine protein 13.4 g/day (<1.0 g/day prior to Nivolumab). Due to concern for reactivation of primary MN vs other causes, he underwent a renal biopsy which revealed chronic reactivated primary MN with strongly positive PLA2R stain. Consideration of immunosuppressive treatment options were discussed, and the patient was initiated on rituximab (1 g IV on Day 1 and 15), a monoclonal antibody binding specifically to CD20 on B cells. Labs one month later showed a Cr of 1.01 mg/dl, decrease in proteinuria by over 50% (4.6 g/day), and improved albumin to 2.9 g/dl. The patient restarted nivolumab in January 2020 and has stable to improved kidney function five months later. PET/CT imaging continues to demonstrate complete metabolic response and no new sites of increased FDG activity.

Discussion

Current guidelines for primary MN recommend therapy with cyclophosphamide and steroids, rituximab, or cyclosporine. All except for rituximab (in)directly suppress T cell function potentially impacting the anti-tumor effectiveness of ICI therapy. While the role(s) of B cells as pro- or anti-tumoral mediators in cancer and ICI is unknown, understanding B cell role(s) could be beneficial for those with autoimmune disease – allowing for split treatment should irAEs occur. Therapy for autoimmune reactivation should be directed by immunosuppressive mechanism in concert with goals of cancer treatment.