Acute interstitial nephritis, a potential predictor of response to immune checkpoint inhibitors in renal cell carcinoma
Autor: | Renée M. McKay, Ivan Pedrosa, Roy Elias, James Brugarolas, Viral M. Patel, Payal Kapur, William Schwartzman, Qi Cai, Alana Christie, Venkat S. Malladi, Miguel Vazquez, Raquibul Hannan, Joseph Formella, Hans J. Hammers |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Oncology Male Cancer Research medicine.medical_specialty Immunology Renal function Ipilimumab Case Report 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Antineoplastic Agents Immunological Renal cell carcinoma Internal medicine medicine Immunology and Allergy Humans kidney neoplasms Adverse effect Carcinoma Renal Cell Immune Checkpoint Inhibitors RC254-282 Aged Pharmacology Creatinine business.industry Melanoma autoimmunity Neoplasms. Tumors. Oncology. Including cancer and carcinogens Middle Aged medicine.disease 2518 1619 030104 developmental biology chemistry 030220 oncology & carcinogenesis Acute Disease Molecular Medicine Nephritis Interstitial Female immunotherapy Nivolumab business Kidney cancer medicine.drug |
Zdroj: | Journal for Immunotherapy of Cancer Journal for ImmunoTherapy of Cancer, Vol 8, Iss 2 (2020) |
ISSN: | 2051-1426 |
Popis: | Immune checkpoint inhibitors (ICIs) such as nivolumab and ipilimumab have improved outcomes in metastatic renal cell carcinoma (mRCC) patients, but they are also associated with immune-related adverse events (irAEs). As observed in melanoma, we hypothesized that patients experiencing an autoimmune reaction directed against the tissue of origin may be more likely to benefit from ICI. Specifically, we asked whether patients with immune-related acute interstitial nephritis (irAIN) exhibited improved outcomes. Using Kidney Cancer Explorer (KCE), a data portal and i2b2-based central database for clinical, pathological and experimental genetic data, we systematically identified all patients with mRCC at UT Southwestern Medical Center (UTSW) from 2014–2018 who received at least one dose of ICI. More recent cases were identified through a provider query. We extracted creatinine (Cr) values at baseline and over the entirety of each patient ICI treatment course using KCE. Patients with ≥ 1.5-fold Cr increase over baseline were investigated. The likelihood of irAIN was determined based on the work-up (biopsy, if available), or by clinical criteria (timing of kidney injury, exclusion of other etiologies, treatment with immunosuppressants and response). We identified 177 mRCC patients who received at least one dose of ICI, 36 of whom had ≥ 1.5-fold increase in Cr over baseline while on treatment. Of those, two had biopsy-proven irAIN and one was clinically diagnosed, resulting in an incidence of 1.7%. One additional biopsy-proven case past 2018 was identified through a provider query, for a total of four patients. Two received combination nivolumab and ipilimumab in the first line, whereas the remaining received nivolumab after first line therapy. irAIN onset ranged from 1.5 to 12 months. All four patients stopped ICI with recovery of renal function, at least partially, three after receiving systemic steroids. Notably, all four patients had a deep response. In conclusion, irAIN is a rare event, but it may portend a higher likelihood of response. One possible explanation is antigenic overlap between normal renal tubular cells and tumor cells. |
Databáze: | OpenAIRE |
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