Immune checkpoint inhibitor associated reactivation of primary membranous nephropathy responsive to rituximab

Our plain-English summary of Immune checkpoint inhibitor associated reactivation of primary membranous nephropathy responsive to rituximab, by J.S. Lin, D.Y. Wang, O. Mamlouk, et al (Journal for Immunotherapy of Cancer, 2020).

The study

• Authors: J.S. Lin, D.Y. Wang, O. Mamlouk, W.F. Glass, M. Abdelrahim, C. Yee, A. Abudayyeh
• Journal: Journal for Immunotherapy of Cancer
• Published: 2020;8(2)
• Type of article: Case report
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The same mechanisms that mediate antitumor immunity from checkpoint inhibitors (CPIs) can also lead to unintended targeting of normal tissues, characterized as immune-related adverse events (irAEs). Those with pre-existing autoimmune disease are believed to be particularly vulnerable for exacerbating underlying autoimmunity or inducing severe irAEs. We report the first case of CPI-associated reactivation of primary membranous nephropathy (MN) in a patient with pleural mesothelioma responding to immunotherapy. Due to its specificity in targeting B-lymphocytes, rituximab was used to treat primary MN with the expectation that this would not interfere with the benefits gained from T cell-mediated antitumor immunity. Rituximab was effective in treating CPI-associated reactivation of MN, and the patient was successfully rechallenged with nivolumab and maintained stable kidney function and sustained clinical antitumor effect. While exacerbation of pre-existing autoimmune diseases from CPIs is common, therapy for autoimmune reactivation can be rationally directed by an understanding of the immunosuppressive mechanism with goals of cancer treatment.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

In plain English

This case report described one 60-year-old man in Texas with malignant pleural mesothelioma (biphasic, predominantly sarcomatoid) and about a 14-year history of primary membranous nephropathy, an antibody-driven kidney disease. The article does not discuss asbestos or his exposure history. He received off-label nivolumab, an immune checkpoint inhibitor. His cancer improved, but his urine protein rose, peaking at 13.4 g/24 hours in November 2019. He also developed type 1 diabetes within a month of starting therapy. A kidney biopsy suggested reactivated primary membranous nephropathy, with a strongly positive PLA2R stain. Nivolumab was paused while he received two 1 g infusions of rituximab, a drug that targets B cells, 14 days apart. One month later his serum creatinine was 1.01 mg/dL, urine protein had fallen by over 50% to 4.6 g/day, and albumin was 2.9 g/dL. He then received five more cycles of nivolumab with stable to improved kidney function, and scans continued to show complete metabolic response. The authors concluded that rituximab was effective in treating the checkpoint inhibitor-associated reactivation of his kidney disease.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (one patient)
• Who was studied: One 60-year-old man with malignant pleural mesothelioma of the right hemithorax, biphasic with predominant sarcomatoid type, diagnosed September 2018. He had a history of primary membranous nephropathy for about 14 years and was seen at the University of Texas MD Anderson Cancer Center nephrology clinic.
• Exposure: The exposure studied was the immune checkpoint inhibitor (anti-PD-1) drug nivolumab, given off-label at 240 mg intravenously every 2 weeks, followed by rituximab treatment. The article does not mention asbestos or any asbestos exposure.
• Main results:
  • After starting nivolumab, the patient's urine protein rose. It peaked at 13.4 g/24 hours in November 2019, having been below 1 g/24 hours before nivolumab.
  • Within 1 month of starting nivolumab, the patient developed diabetic ketoacidosis and checkpoint inhibitor-induced type 1 diabetes.
  • The 2019 kidney biopsy suggested chronic reactivated primary membranous nephropathy, with a strongly positive PLA2R stain.
  • One month after two 1 g rituximab infusions given 14 days apart, the patient's serum creatinine was 1.01 mg/dL, urine protein had fallen by over 50% to 4.6 g/day, and albumin was 2.9 g/dL.
  • The patient then received five cycles of nivolumab after rituximab, with stable to improved kidney function.
  • PET/CT imaging of the patient continued to show complete metabolic response of the cancer.
• The authors' conclusion: The authors concluded that rituximab was effective in treating the checkpoint inhibitor-associated reactivation of primary membranous nephropathy in this patient, who was successfully rechallenged with nivolumab.
• Limitations the authors state:
  • The patient's baseline serum PLA2R level was unavailable, so the undetectable level after rituximab could not be compared with an earlier value.
  • PLA2R testing was not available at the time of the patient's 2011 kidney biopsy.

Topics

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Immune-Related Adverse Events, Pleural Mesothelioma, Immunotherapy, Nivolumab (Opdivo).

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• Immune checkpoint inhibitors a new player in the therapeutic game of mesothelioma: New reality with new challenges — K. Parikh, L.E.L. Hendriks, et al. (2021)
• Primary pericardial mesothelioma: a case report of a patient treated with an immune checkpoint inhibitor as the second-line treatment — O. Arponen, V. Salo, et al. (2021)
• Immune checkpoint inhibitors in non-small cell lung cancer (NSCLC): Approaches on special subgroups and unresolved burning questions — J. Remon, N. Vilariño, et al. (2018)
• Immune checkpoint inhibitors in malignant pleural mesothelioma: promises and challenges — G.L. Ceresoli, M. Bonomi, et al. (2016)

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