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1. Shorter versus longer corticosteroid duration and recurrent immune checkpoint inhibitor-associated AKI

Author

Joe-Elie Salem, Enriqueta Felip, Shuchi Anand, Karolina Benesova, Marlies Ostermann, Ala Abudayyeh, Omar Mamlouk, Umut Selamet, Grace Cherry, Sunandana Chandra, Sandra M Herrmann, Maria Jose Soler, Abhijat Kitchlu, Jamie S Lin, Kerry L Reynolds, Elizabeth M Gaughan, Eva Muñoz-Couselo, Jamie S Hirsch, Pablo Garcia, Meghan E Sise, Thibaud Koessler, Mark Eijgelsheim, Shruti Gupta, Frank B Cortazar, Jason M Prosek, Ilya Glezerman, Shveta S Motwani, Naoka Murakami, Rimda Wanchoo, David I Ortiz-Melo, Arash Rashidi, Ben Sprangers, Vikram Aggarwal, A Bilal Malik, Sebastian Loew, Christopher A Carlos, Pazit Beckerman, Zain Mithani, Chintan V Shah, Amanda D Renaghan, Sophie De Seigneux, Luca Campedel, Daniel Sanghoon Shin, Sunil Rangarajan, Priya Deshpande, Gaia Coppock, Marium Husain, Clara Garcia-Carro, Sheila Bermejo, Nuttha Lumlertgul, Nina Seylanova, Busra Isik, Aydin Kaghazchi, Yuriy Khanin, Sheru K Kansal, Kai M Schmidt-Ott, Raymond K Hsu, Maria C Tio, Harkarandeep Singh, Kenar D Jhaveri, David E Leaf, Corinne Isnard Bagnis, Suraj S Mothi, Weiting Chang, Vipulbhai Sakhiya, Daniel Stalbow, Sylvia Wu, Armando Cennamo, Anne Rigg, Nisha Shaunak, Zoe A Kibbelaar, Harish S Seethapathy, Meghan Lee, Ian A Strohbhen, Ilya G Glezerman, Dwight H Owen, Sharon Mini, Andrey Kisel, Nicole Albert, Katherine Carter, Vicki Donley, Tricia Young, Heather Cigoi, Els Wauters Ben Sprangers, Javier A Pagan, Jonathan J Hogan, Valda Page, Samuel AP Short, Maria Josep Carreras, and Sethu M. Madhavan

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background Corticosteroids are the mainstay of treatment for immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI), but the optimal duration of therapy has not been established. Prolonged use of corticosteroids can cause numerous adverse effects and may decrease progression-free survival among patients treated with ICPis. We sought to determine whether a shorter duration of corticosteroids was equally efficacious and safe as compared with a longer duration.Methods We used data from an international multicenter cohort study of patients diagnosed with ICPi-AKI from 29 centers across nine countries. We examined whether a shorter duration of corticosteroids (28 days or less) was associated with a higher rate of recurrent ICPi-AKI or death within 30 days following completion of corticosteroid treatment as compared with a longer duration (29–84 days).Results Of 165 patients treated with corticosteroids, 56 (34%) received a shorter duration of treatment and 109 (66%) received a longer duration. Patients in the shorter versus longer duration groups were similar with respect to baseline and ICPi-AKI characteristics. Five of 56 patients (8.9%) in the shorter duration group and 12 of 109 (11%) in the longer duration group developed recurrent ICPi-AKI or died (p=0.90). Nadir serum creatinine in the first 14, 28, and 90 days following completion of corticosteroid treatment was similar between groups (p=0.40, p=0.56, and p=0.89, respectively).Conclusion A shorter duration of corticosteroids (28 days or less) may be safe for patients with ICPi-AKI. However, the findings may be susceptible to unmeasured confounding and further research from randomized clinical trials is needed.

Published
2022
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2. Acute kidney injury in patients treated with immune checkpoint inhibitors

Author

Joe-Elie Salem, Enriqueta Felip, Sophie Papa, Shuchi Anand, Karolina Benesova, Marlies Ostermann, Ala Abudayyeh, Omar Mamlouk, Umut Selamet, Grace Cherry, Sunandana Chandra, Sandra M Herrmann, Maria Jose Soler, Abhijat Kitchlu, Jamie S Lin, Kerry L Reynolds, Osama E Rahma, Elizabeth M Gaughan, Eva Muñoz-Couselo, Jamie S Hirsch, Pablo Garcia, Meghan D Lee, Harish Seethapathy, Ian A Strohbehn, Meghan E Sise, Wei-Ting Chang, Els Wauters, Lucy Flanders, Deborah Schrag, Thibaud Koessler, Mark Eijgelsheim, Shruti Gupta, Frank B Cortazar, Samuel A P Short, Jason M Prosek, Sethu M Madhavan, Ilya Glezerman, Shveta S Motwani, Naoka Murakami, Rimda Wanchoo, David I Ortiz-Melo, Arash Rashidi, Ben Sprangers, Vikram Aggarwal, A Bilal Malik, Sebastian Loew, Christopher A Carlos, Pazit Beckerman, Zain Mithani, Chintan V Shah, Amanda D Renaghan, Sophie De Seigneux, Luca Campedel, Daniel Sanghoon Shin, Sunil Rangarajan, Priya Deshpande, Gaia Coppock, Dwight H. Owen, Marium Husain, Clara Garcia-Carro, Sheila Bermejo, Nuttha Lumlertgul, Nina Seylanova, Busra Isik, Aydin Kaghazchi, Yuriy Khanin, Sheru K Kansal, Kai M Schmidt-Ott, Raymond K Hsu, Maria C Tio, Suraj Sarvode Mothi, Harkarandeep Singh, Kenar D Jhaveri, David E Leaf, Corinne Isnard Bagnis, Suraj S Mothi, Weiting Chang, Vipulbhai Sakhiya, Daniel Stalbow, Sylvia Wu, Armando Cennamo, Anne Rigg, Nisha Shaunak, Zoe A Kibbelaar, Harish S Seethapathy, Meghan Lee, Ian A Strohbhen, Ilya G Glezerman, Dwight H Owen, Sharon Mini, Andrey Kisel, Nicole Albert, Katherine Carter, Vicki Donley, Tricia Young, Heather Cigoi, Els Wauters Ben Sprangers, Javier A Pagan, Jonathan J Hogan, Valda Page, Samuel AP Short, and Maria Josep Carreras

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.Methods We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.Results ICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.Conclusions Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

Published
2021
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3. Acute kidney injury in patients receiving pembrolizumab combination therapy versus pembrolizumab monotherapy for advanced lung cancer

Author

Shruti Gupta, Ian A. Strohbehn, Qiyu Wang, Paul E. Hanna, Rituvanthikaa Seethapathy, Jason M. Prosek, Sandra M. Herrmann, Ala Abudayyeh, A. Bilal Malik, Sebastian Loew, Christopher A. Carlos, Wei-Ting Chang, Pazit Beckerman, Zain Mithani, Chintan V. Shah, Amanda D. Renaghan, Sophie de Seigneux, Luca Campedel, Abhijat Kitchlu, Daniel Sanghoon Shin, Gaia Coppock, Nuttha Lumlertgul, Pablo Garcia, David I. Ortiz-Melo, Arash Rashidi, Ben Sprangers, Vikram Aggarwal, Karolina Benesova, Kenar D. Jhaveri, Frank B. Cortazar, Astrid Weins, Yiqin Zuo, Meghan J. Mooradian, Kerry L. Reynolds, David E. Leaf, Meghan E. Sise, Joe-Elie Salem, Corinne Isnard Bagnis, Harkarandeep Singh, Shveta S. Motwani, Naoka Murakami, Maria C. Tio, Suraj S. Mothi, Umut Selamet, Kai M. Schmidt-Ott, Weiting Chang, Rimda Wanchoo, Yuriy Khanin, Jamie S. Hirsch, Vipulbhai Sakhiya, Daniel Stalbow, Sylvia Wu, Marlies Ostermann, Nina Seylanova, Armando Cennamo, Anne Rigg, Nisha Shaunak, Zoe A. Kibbelaar, Priya Deshpande, Harish S. Seethapathy, Meghan Lee, Ian A. Strohbhen, Busra Isik, Ilya G. Glezerman, Sunandana Chandra, Sethu M. Madhavan, Dwight H. Owen, Marium Husain, Sharon Mini, Shuchi Anand, Aydin Kaghazchi, Sunil Rangarajan, Grace Cherry, Raymond K. Hsu, Andrey Kisel, Sheru K. Kansal, Nicole Albert, Katherine Carter, Vicki Donley, Tricia Young, Heather Cigoi, Sophie De Seigneux, Thibaud Koessler, Els Wauters, Mark Eijgelsheim, Javier A. Pagan, Jonathan J. Hogan, Omar Mamlouk, Jamie S. Lin, Valda Page, Samuel A.P. Short, Elizabeth M. Gaughan, Maria Jose Soler, Clara García-Carro, Sheila Bermejo, Enriqueta Felip, Eva Muñoz-Couselo, and Maria Josep Carreras

Subjects
Lung Neoplasms, Nephrology, Antineoplastic Combined Chemotherapy Protocols, Humans, Acute Kidney Injury, Antibodies, Monoclonal, Humanized
Published
2022

4. Acute kidney injury in patients treated with immune checkpoint inhibitors

Author

Enriqueta Felip, Sophie Papa, Shuchi Anand, Karolina Benesova, Ala Abudayyeh, Omar Mamlouk, Umut Selamet, Grace Cherry, Sunandana Chandra, Sandra M Herrmann, Maria Jose Soler, Abhijat Kitchlu, Jamie S Lin, Kerry L Reynolds, Osama E Rahma, Elizabeth M Gaughan, Eva Muñoz-Couselo, Jamie S Hirsch, Pablo Garcia, Meghan D Lee, Harish Seethapathy, Ian A Strohbehn, Meghan E Sise, Wei-Ting Chang, Els Wauters, Lucy Flanders, Deborah Schrag, Thibaud Koessler, Mark Eijgelsheim, Shruti Gupta, Frank B Cortazar, Samuel A P Short, Jason M Prosek, Sethu M Madhavan, Ilya Glezerman, Shveta S Motwani, Naoka Murakami, Rimda Wanchoo, David I Ortiz-Melo, Arash Rashidi, Ben Sprangers, Vikram Aggarwal, A Bilal Malik, Sebastian Loew, Christopher A Carlos, Pazit Beckerman, Zain Mithani, Chintan V Shah, Amanda D Renaghan, Sophie De Seigneux, Luca Campedel, Daniel Sanghoon Shin, Sunil Rangarajan, Priya Deshpande, Gaia Coppock, Dwight H. Owen, Marium Husain, Clara Garcia-Carro, Sheila Bermejo, Nuttha Lumlertgul, Nina Seylanova, Busra Isik, Aydin Kaghazchi, Yuriy Khanin, Sheru K Kansal, Kai M Schmidt-Ott, Raymond K Hsu, Maria C Tio, Suraj Sarvode Mothi, Harkarandeep Singh, Kenar D Jhaveri, David E Leaf, Corinne Isnard Bagnis, Suraj S Mothi, Weiting Chang, Vipulbhai Sakhiya, Daniel Stalbow, Sylvia Wu, Armando Cennamo, Anne Rigg, Nisha Shaunak, Zoe A Kibbelaar, Harish S Seethapathy, Meghan Lee, Ian A Strohbhen, Ilya G Glezerman, Dwight H Owen, Sharon Mini, Andrey Kisel, Nicole Albert, Katherine Carter, Vicki Donley, Tricia Young, Heather Cigoi, Els Wauters Ben Sprangers, Javier A Pagan, Jonathan J Hogan, Valda Page, Samuel AP Short, Maria Josep Carreras, Institut Català de la Salut, [Gupta S] Division of Renal Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA. [Short SAP] University of Vermont Larner College of Medicine, Burlington, Vermont, USA. [Sise ME] Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA. [Prosek JM, Madhavan SM] Division of Nephrology, Department of Internal Medicine, The Ohio State University Medical Center, Columbus, Ohio, USA. [Soler MJ, Bermejo S] Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Ostermann M] Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Nephrology Department, San Carlos Clinical University Hospital, Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, Cancer Research, ACUTE INTERSTITIAL NEPHRITIS, Immunoteràpia, Other subheadings::Other subheadings::/drug therapy [Other subheadings], urologic and male genital diseases, THERAPY, Gastroenterology, Cohort Studies, Risk Factors, Immunology and Allergy, Immune Checkpoint Inhibitors, RC254-282, RISK, Clinical/Translational Cancer Immunotherapy, Kidney, medicine.diagnostic_test, terapéutica::terapia biológica::inmunomodulación::inmunoterapia [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Acute kidney injury, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Acute Kidney Injury, Middle Aged, female genital diseases and pregnancy complications, medicine.anatomical_structure, Oncology, Molecular Medicine, Female, immunotherapy, Life Sciences & Biomedicine, CTLA-4 antigen, medicine.medical_specialty, enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales::insuficiencia renal::lesión renal aguda [ENFERMEDADES], medicine.drug_class, Immunology, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Proton-pump inhibitor, Renal function, programmed cell death 1 receptor, EVENTS, Internal medicine, Biopsy, medicine, Humans, Adverse effect, Acute tubulointerstitial nephritis, Aged, Pharmacology, Science & Technology, Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], urogenital system, business.industry, Proportional hazards model, CLINICAL-FEATURES, medicine.disease, Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Acute Kidney Injury [DISEASES], business, Ronyons - Malalties - Tractament
Abstract

BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.ResultsICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.ConclusionsPatients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

Published
2021

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