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Safety and efficacy of anti-PD-1 in patients with baseline cardiac, renal, or hepatic dysfunction

BACKGROUND: Anti-PD-1 therapy is increasingly used in various advanced malignancies. Patients with baseline organ dysfunction are largely excluded from clinical trials. Therefore it is unclear whether anti-PD-1 therapy is safe or effective in this setting. Further, these patients are often not candi...

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Autores principales: Kanz, Bridgette A., Pollack, Megan H., Johnpulle, Romany, Puzanov, Igor, Horn, Leora, Morgans, Alicia, Sosman, Jeffrey A., Rapisuwon, Suthee, Conry, R. Martin, Eroglu, Zeynep, Johnson, Douglas B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067899/
https://www.ncbi.nlm.nih.gov/pubmed/27777770
http://dx.doi.org/10.1186/s40425-016-0166-5
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author Kanz, Bridgette A.
Pollack, Megan H.
Johnpulle, Romany
Puzanov, Igor
Horn, Leora
Morgans, Alicia
Sosman, Jeffrey A.
Rapisuwon, Suthee
Conry, R. Martin
Eroglu, Zeynep
Johnson, Douglas B.
author_facet Kanz, Bridgette A.
Pollack, Megan H.
Johnpulle, Romany
Puzanov, Igor
Horn, Leora
Morgans, Alicia
Sosman, Jeffrey A.
Rapisuwon, Suthee
Conry, R. Martin
Eroglu, Zeynep
Johnson, Douglas B.
author_sort Kanz, Bridgette A.
collection PubMed
description BACKGROUND: Anti-PD-1 therapy is increasingly used in various advanced malignancies. Patients with baseline organ dysfunction are largely excluded from clinical trials. Therefore it is unclear whether anti-PD-1 therapy is safe or effective in this setting. Further, these patients are often not candidates for other anti-cancer therapies, highlighting their need for active treatment options. METHODS: We performed a retrospective analysis of patients from multiple centers with advanced solid tumors and baseline organ dysfunction who received anti-PD-1 therapy. Organ dysfunction was defined as cardiac (left ventricular ejection fraction ≤45 %), renal (creatinine ≥2 mg/dL or GFR ≤30 ml/min) or hepatic dysfunction (evidence of cirrhosis on imaging or AST, ALT or bilirubin ≥3x ULN). We assessed change in organ dysfunction, immune related adverse events (irAEs), response rate, progression free survival (PFS) and overall survival (OS). RESULTS: We identified 27 patients eligible for inclusion with the following diseases: renal cell carcinoma (n = 8), melanoma (10), non-small cell lung cancer (3), small cell lung cancer (2) and urothelial bladder cancer (4). Baseline organ dysfunction included renal dysfunction (n = 17), hepatic dysfunction (7), cardiac dysfunction (11), including >1 organ dysfunction (8). Worsening organ dysfunction requiring hospitalization or dose delays occurred in 8 patients (30 %) although in most cases this was thought not-drug related and resolved with supportive care. Grade 3 irAEs occurred in 2 pts (7 %; hepatitis and colitis). Thirteen of 27 patients had ongoing treatment benefit (objective response or stable disease) at data collection (48 %). Eleven patients had primary progressive disease (41 %), 11 had stable disease (41 %), 4 had partial responses (15 %), and one had a complete response (4 %). Overall, median PFS was 168 days. Median OS was not reached. CONCLUSIONS: In our experience, anti-PD-1 agents in this group of patients with cardiac, hepatic or renal dysfunction were associated with tolerable irAEs and infrequent manageable worsening of organ dysfunction. Further, objective responses and prolonged PFS were observed in a number of patients. Thus, patients with baseline organ dysfunction may be considered for anti-PD-1 therapy with appropriate clinical monitoring.
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spelling pubmed-50678992016-10-24 Safety and efficacy of anti-PD-1 in patients with baseline cardiac, renal, or hepatic dysfunction Kanz, Bridgette A. Pollack, Megan H. Johnpulle, Romany Puzanov, Igor Horn, Leora Morgans, Alicia Sosman, Jeffrey A. Rapisuwon, Suthee Conry, R. Martin Eroglu, Zeynep Johnson, Douglas B. J Immunother Cancer Research Article BACKGROUND: Anti-PD-1 therapy is increasingly used in various advanced malignancies. Patients with baseline organ dysfunction are largely excluded from clinical trials. Therefore it is unclear whether anti-PD-1 therapy is safe or effective in this setting. Further, these patients are often not candidates for other anti-cancer therapies, highlighting their need for active treatment options. METHODS: We performed a retrospective analysis of patients from multiple centers with advanced solid tumors and baseline organ dysfunction who received anti-PD-1 therapy. Organ dysfunction was defined as cardiac (left ventricular ejection fraction ≤45 %), renal (creatinine ≥2 mg/dL or GFR ≤30 ml/min) or hepatic dysfunction (evidence of cirrhosis on imaging or AST, ALT or bilirubin ≥3x ULN). We assessed change in organ dysfunction, immune related adverse events (irAEs), response rate, progression free survival (PFS) and overall survival (OS). RESULTS: We identified 27 patients eligible for inclusion with the following diseases: renal cell carcinoma (n = 8), melanoma (10), non-small cell lung cancer (3), small cell lung cancer (2) and urothelial bladder cancer (4). Baseline organ dysfunction included renal dysfunction (n = 17), hepatic dysfunction (7), cardiac dysfunction (11), including >1 organ dysfunction (8). Worsening organ dysfunction requiring hospitalization or dose delays occurred in 8 patients (30 %) although in most cases this was thought not-drug related and resolved with supportive care. Grade 3 irAEs occurred in 2 pts (7 %; hepatitis and colitis). Thirteen of 27 patients had ongoing treatment benefit (objective response or stable disease) at data collection (48 %). Eleven patients had primary progressive disease (41 %), 11 had stable disease (41 %), 4 had partial responses (15 %), and one had a complete response (4 %). Overall, median PFS was 168 days. Median OS was not reached. CONCLUSIONS: In our experience, anti-PD-1 agents in this group of patients with cardiac, hepatic or renal dysfunction were associated with tolerable irAEs and infrequent manageable worsening of organ dysfunction. Further, objective responses and prolonged PFS were observed in a number of patients. Thus, patients with baseline organ dysfunction may be considered for anti-PD-1 therapy with appropriate clinical monitoring. BioMed Central 2016-10-18 /pmc/articles/PMC5067899/ /pubmed/27777770 http://dx.doi.org/10.1186/s40425-016-0166-5 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Kanz, Bridgette A.
Pollack, Megan H.
Johnpulle, Romany
Puzanov, Igor
Horn, Leora
Morgans, Alicia
Sosman, Jeffrey A.
Rapisuwon, Suthee
Conry, R. Martin
Eroglu, Zeynep
Johnson, Douglas B.
Safety and efficacy of anti-PD-1 in patients with baseline cardiac, renal, or hepatic dysfunction
title Safety and efficacy of anti-PD-1 in patients with baseline cardiac, renal, or hepatic dysfunction
title_full Safety and efficacy of anti-PD-1 in patients with baseline cardiac, renal, or hepatic dysfunction
title_fullStr Safety and efficacy of anti-PD-1 in patients with baseline cardiac, renal, or hepatic dysfunction
title_full_unstemmed Safety and efficacy of anti-PD-1 in patients with baseline cardiac, renal, or hepatic dysfunction
title_short Safety and efficacy of anti-PD-1 in patients with baseline cardiac, renal, or hepatic dysfunction
title_sort safety and efficacy of anti-pd-1 in patients with baseline cardiac, renal, or hepatic dysfunction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067899/
https://www.ncbi.nlm.nih.gov/pubmed/27777770
http://dx.doi.org/10.1186/s40425-016-0166-5
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