Pembrolizumab-associated minimal change disease in a patient with malignant pleural mesothelioma

Our plain-English summary of Pembrolizumab-associated minimal change disease in a patient with malignant pleural mesothelioma, by A. Bickel, I. Koneth, A. Enzler-Tschudy, et al (BMC Cancer, 2016).

The study

• Authors: A. Bickel, I. Koneth, A. Enzler-Tschudy, J. Neuweiler, L. Flatz, M. Früh
• Journal: BMC Cancer
• Published: 2016;16:656
• Type of article: Case report
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pembrolizumab is an anti- Programmed Death 1 (PD-1) antibody approved in melanoma, non-small cell lung cancer and investigated in malignant pleural mesothelioma. The most frequent immunotherapy related autoimmune reactions include dermatitis, pneumonitis, colitis, hypophysitis, uveitis, hypothyreodism, hepatitis and interstitial nephritis.

Case Presentation: We describe a 62-year old patient diagnosed with malignant pleural mesothelioma who experienced ten days after the second dose of third line therapy with pembrolizumab sudden onset of generalized edema including legs and eyelids and weight gain of 15 kg resulting from nephrotic syndrome and acute renal failure. Pembrolizumab was discontinued and prednisone, diuretics and angiotensin II receptor blocker were initiated with full recovery of symptoms and renal function. Pembrolizumab-associated minimal change disease (MCD) was confirmed by electron microscopy in the renal biopsy.

Conclusion: We are the first to describe pembrolizumab-related minimal change disease (MCD). Physicians should be aware of this side effect in patients presenting with edema and weight gain and initiate prompt renal function testing, serum albumin and urinalysis followed by steroid treatment if pembrolizumab-related MCD is suspected.

In plain English

This case report described one 62-year-old patient diagnosed in June 2014 with malignant biphasic pleural mesothelioma. The article does not mention asbestos exposure. After the disease progressed on carboplatin/pemetrexed and then vinorelbine, the patient received third-line treatment with pembrolizumab, an immunotherapy drug. Ten days after the second 200 mg dose, the patient developed sudden swelling of the legs and eyelids and gained 15 kg. Doctors diagnosed nephrotic syndrome (urine protein 19 g per day, blood albumin 15 g/l, cholesterol 7.8 mmol/l). Acute kidney failure followed, with estimated kidney filtration falling from above 90 to 28 ml/min/1.73 m2. Pembrolizumab was stopped, and prednisone, diuretics and an angiotensin II receptor blocker were started. Electron microscopy of a kidney biopsy showed changes compatible with minimal change disease. Within 5 weeks, creatinine values normalized and the protein loss resolved. Ten weeks later the patient remained stable without systemic therapy. The authors concluded that, to their knowledge, this was the first case of pembrolizumab-associated minimal change disease, and that physicians should be aware of this side effect.

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 62-year-old patient diagnosed with malignant biphasic pleural mesothelioma in June 2014; the authors are from the Cantonal Hospital St. Gallen, Switzerland
• Exposure: Pembrolizumab (anti-PD-1 antibody), 200 mg doses, given as third-line therapy after six cycles of carboplatin/pemetrexed and six cycles of vinorelbine. No asbestos exposure is described.
• Main results:
  • Ten days after the second pembrolizumab dose, the patient had sudden generalized edema (legs and eyelids) and gained 15 kg
  • Nephrotic syndrome was diagnosed in the patient: proteinuria of 19 g per day, hypoalbuminemia (15 g/l) and hypercholesterolemia of 7.8 mmol/l
  • Acute renal failure followed: the patient's estimated glomerular filtration rate fell from above 90 to 28 ml/min/1.73 m2
  • Electron microscopy of the renal biopsy showed diffuse fusion of the epithelial foot processes, compatible with minimal change disease; direct immunofluorescence was negative
  • After pembrolizumab was stopped and prednisone, diuretics and an angiotensin II receptor blocker were given, the patient's creatinine normalized and proteinuria resolved within 5 weeks
  • The patient remained in stable condition without systemic therapy 10 weeks later
• The authors' conclusion: The authors stated that, to the best of their knowledge, this is the first case of pembrolizumab-associated minimal change disease resulting in nephrotic syndrome and acute renal failure. They said physicians should be aware of this side effect in patients presenting with edema and weight gain.
• Limitations the authors state:
  • The authors stated that whether a structural and functional similarity between kidney podocytes and mesothelial cells increases the risk of minimal change disease with immunotherapy in mesothelioma patients would have to be further investigated

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pembrolizumab (Keytruda), Pleural Mesothelioma, Non-Small Cell Lung Cancer, Immunotherapy, Pneumonitis, Interstitial, Biopsy.

Related studies

• Pembrolizumab-Associated CD8+ Vasculitic Mononeuritis Multiplex in a Patient With Mesothelioma — M.C. Baldauf, M. Kapauer, et al. (2021)
• Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study — A. Marabelle, M. Fakih, et al. (2020)
• Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial — E.W. Alley, J. Lopez, et al. (2017)
• Pembrolizumab in paediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumour or lymphoma (KEYNOTE-051): interim analysis of an open-label, single-arm, phase 1-2 trial — B. Geoerger, H.J. Kang, et al. (2020)
• Efficacy and safety of pembrolizumab in patients with advanced mesothelioma in the open-label, single-arm, phase 2 KEYNOTE-158 study — T.A. Yap, K. Nakagawa, et al. (2021)
• Prospective real-world study on the pharmacokinetics of pembrolizumab in patients with solid tumors — D.P. Hurkmans, S.D.T. Sassen, et al. (2021)

Browse more research in BMC Cancer, or return to medical research.