Response to combined ipilimumab and nivolumab after development of a nephrotic syndrome related to PD-1 monotherapy

Background High response rates of metastatic melanoma have been reported upon immune checkpoint inhibition by PD-1 blockade alone or in combination with CTLA-4 inhibitors. However, the majority of patients with a primary resistance to anti-PD-1 monotherapy is also refractory to a subsequent combined...

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Bibliographic Details
Published in:	Journal for immunotherapy of cancer Vol. 7; no. 1; pp. 181 - 5
Main Authors:	Glutsch, Valerie, Grän, Franziska, Weber, Judith, Gesierich, Anja, Goebeler, Matthias, Schilling, Bastian
Format:	Journal Article
Language:	English
Published:	London BioMed Central 12.07.2019 BioMed Central Ltd BMJ Publishing Group LTD BMJ Publishing Group
Subjects:	Abdomen Acute kidney failure Aged Antibodies Antineoplastic Agents, Immunological - adverse effects Antineoplastic Agents, Immunological - therapeutic use Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biopsy Cancer Cancer metastasis Case Report Case Reports CAT scans Consent Creatinine Dehydrogenases Development and progression Disease Diuretics Dosage and administration Drug Substitution Drug therapy Edema Funding Humans Immune checkpoint inhibitors Immune-related adverse event Immunology Immunotherapy Ipilimumab Ipilimumab - administration & dosage Kidney diseases Kidney failure Kidney Function Tests Kidneys Lymphatic system Male Medical imaging Medical research Medicine Medicine & Public Health Melanoma Melanoma - complications Melanoma - diagnosis Melanoma - drug therapy Metastasis Microscopy Minimal change disease Molecular Targeted Therapy - adverse effects Monoclonal antibodies Nephritis Nephrotic syndrome Nephrotic Syndrome - diagnosis Nephrotic Syndrome - etiology Nivolumab Nivolumab - administration & dosage Oncology Oral drugs Patients PD-1 Pharmaceuticals Programmed Cell Death 1 Receptor - antagonists & inhibitors Proteins Skin cancer Targeted cancer therapy Treatment Outcome Tumors Urine Minimal change disease Immune-related adverse event PD-1 Ipilimumab Nivolumab
ISSN:	2051-1426, 2051-1426
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Summary:	Background High response rates of metastatic melanoma have been reported upon immune checkpoint inhibition by PD-1 blockade alone or in combination with CTLA-4 inhibitors. However, the majority of patients with a primary resistance to anti-PD-1 monotherapy is also refractory to a subsequent combined checkpoint inhibition. In BRAF wildtype patients with a primary resistance to PD-1 inhibitors, therapeutic options are therefore limited and immune-related adverse events (irAE) have to be taken into consideration when discussing a subsequent immunotherapy. Case presentation We report the case of a 68-year-old male patient with metastatic melanoma who experienced an acute renal failure with nephrotic syndrome due to a minimal change disease developing after a single dose of the anti-PD-1 antibody pembrolizumab. A kidney biopsy revealed a podocytopathy without signs of interstitial nephritis. Renal function recovered to almost normal creatinine and total urine protein levels upon treatment with oral steroids and diuretics. Unfortunately, a disease progression (PD, RECIST 1.1) was observed in a CT scan after resolution of the irAE. In a grand round, re-exposure to a PD-1-containing regime was recommended. Consensually, a combined immunotherapy with ipilimumab and nivolumab was initiated. Nephrotoxicity was tolerable during combined immunotherapy and a CT scan of chest and abdomen showed a deep partial remission (RECIST 1.1) after three doses of ipilimumab (3 mg/kg) and nivolumab (1 mg/kg). Conclusion This case illustrates that a fulminant response to combined checkpoint inhibition is possible after progression after anti-PD-1 monotherapy and a severe irAE.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Case Study-2 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3
ISSN:	2051-1426 2051-1426
DOI:	10.1186/s40425-019-0655-4