Cargando…

Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC

INTRODUCTION: The development of immune-related adverse events (irAEs) has been associated with improved efficacy of immune checkpoint inhibitors in patients with urothelial cancer, melanoma, and NSCLC. Whether this association exists in patients with SCLC is currently unknown. METHODS: We conducted...

Descripción completa

Detalles Bibliográficos
Autores principales: Ricciuti, Biagio, Naqash, Abdul Rafeh, Naidoo, Jarushka, Sehgal, Kartik, Miller, Adam, Kehl, Kenneth, Venkatraman, Deepti, Sands, Jacob, Lamberti, Giuseppe, Recondo, Gonzalo, Zhang, Jiajia, Macherla, Shravanti, Baig, Sameer, Walker, Paul, Rangachari, Deepa, Gainor, Justin F., Costa, Daniel B., Rizvi, Naiyer, Sholl, Lynette M., Nishino, Mizuki, Henick, Brian, Farago, Anna F., Awad, Mark M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474257/
https://www.ncbi.nlm.nih.gov/pubmed/34589955
http://dx.doi.org/10.1016/j.jtocrr.2020.100074
_version_ 1784575172410343424
author Ricciuti, Biagio
Naqash, Abdul Rafeh
Naidoo, Jarushka
Sehgal, Kartik
Miller, Adam
Kehl, Kenneth
Venkatraman, Deepti
Sands, Jacob
Lamberti, Giuseppe
Recondo, Gonzalo
Zhang, Jiajia
Macherla, Shravanti
Baig, Sameer
Walker, Paul
Rangachari, Deepa
Gainor, Justin F.
Costa, Daniel B.
Rizvi, Naiyer
Sholl, Lynette M.
Nishino, Mizuki
Henick, Brian
Farago, Anna F.
Awad, Mark M.
author_facet Ricciuti, Biagio
Naqash, Abdul Rafeh
Naidoo, Jarushka
Sehgal, Kartik
Miller, Adam
Kehl, Kenneth
Venkatraman, Deepti
Sands, Jacob
Lamberti, Giuseppe
Recondo, Gonzalo
Zhang, Jiajia
Macherla, Shravanti
Baig, Sameer
Walker, Paul
Rangachari, Deepa
Gainor, Justin F.
Costa, Daniel B.
Rizvi, Naiyer
Sholl, Lynette M.
Nishino, Mizuki
Henick, Brian
Farago, Anna F.
Awad, Mark M.
author_sort Ricciuti, Biagio
collection PubMed
description INTRODUCTION: The development of immune-related adverse events (irAEs) has been associated with improved efficacy of immune checkpoint inhibitors in patients with urothelial cancer, melanoma, and NSCLC. Whether this association exists in patients with SCLC is currently unknown. METHODS: We conducted a multicenter retrospective study to evaluate the relationship between irAEs and immunotherapy efficacy in SCLC. To account for the lead-time bias resulting from the time-dependent nature of irAEs, the development of irAEs was considered as a time-varying covariate in univariate and multivariate Cox proportional hazard models. RESULTS: Of the 183 patients treated with immunotherapy, 73 (39.9%) experienced at least one irAE. A total of 42 patients (22.9%) had grade 1 to 2 irAEs, whereas 31 patients (16.9%) had grade 3 to 4 irAEs. The median time of onset to the first irAE was 24 days (interquartile range: 14–55). The baseline clinicopathologic features were well-balanced between patients with and without irAEs. At a median follow-up of 24 months (95% confidence interval [CI]: 17.0–31.6), the median progression-free survival was significantly longer in the irAE group than the non-irAE group (3.8 versus 1.3 mo, p < 0.0001). The median overall survival was also significantly longer among patients with irAEs than patients without irAEs (13.8 versus 2.9 mo, p < 0.0001). When analyzed as a time-varying covariate, the development of irAEs was associated with a significant improvement in progression-free survival (hazard ratio: 0.44 [95% CI: 0.29–0.66], p < 0.001) and overall survival (hazard ratio: 0.47 [95% CI: 0.32–0.71], p < 0.001) in multivariate models. CONCLUSIONS: The development of irAEs is associated with improved clinical outcomes for immunotherapy in patients with advanced SCLC.
format Online
Article
Text
id pubmed-8474257
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-84742572021-09-28 Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC Ricciuti, Biagio Naqash, Abdul Rafeh Naidoo, Jarushka Sehgal, Kartik Miller, Adam Kehl, Kenneth Venkatraman, Deepti Sands, Jacob Lamberti, Giuseppe Recondo, Gonzalo Zhang, Jiajia Macherla, Shravanti Baig, Sameer Walker, Paul Rangachari, Deepa Gainor, Justin F. Costa, Daniel B. Rizvi, Naiyer Sholl, Lynette M. Nishino, Mizuki Henick, Brian Farago, Anna F. Awad, Mark M. JTO Clin Res Rep Original Article INTRODUCTION: The development of immune-related adverse events (irAEs) has been associated with improved efficacy of immune checkpoint inhibitors in patients with urothelial cancer, melanoma, and NSCLC. Whether this association exists in patients with SCLC is currently unknown. METHODS: We conducted a multicenter retrospective study to evaluate the relationship between irAEs and immunotherapy efficacy in SCLC. To account for the lead-time bias resulting from the time-dependent nature of irAEs, the development of irAEs was considered as a time-varying covariate in univariate and multivariate Cox proportional hazard models. RESULTS: Of the 183 patients treated with immunotherapy, 73 (39.9%) experienced at least one irAE. A total of 42 patients (22.9%) had grade 1 to 2 irAEs, whereas 31 patients (16.9%) had grade 3 to 4 irAEs. The median time of onset to the first irAE was 24 days (interquartile range: 14–55). The baseline clinicopathologic features were well-balanced between patients with and without irAEs. At a median follow-up of 24 months (95% confidence interval [CI]: 17.0–31.6), the median progression-free survival was significantly longer in the irAE group than the non-irAE group (3.8 versus 1.3 mo, p < 0.0001). The median overall survival was also significantly longer among patients with irAEs than patients without irAEs (13.8 versus 2.9 mo, p < 0.0001). When analyzed as a time-varying covariate, the development of irAEs was associated with a significant improvement in progression-free survival (hazard ratio: 0.44 [95% CI: 0.29–0.66], p < 0.001) and overall survival (hazard ratio: 0.47 [95% CI: 0.32–0.71], p < 0.001) in multivariate models. CONCLUSIONS: The development of irAEs is associated with improved clinical outcomes for immunotherapy in patients with advanced SCLC. Elsevier 2020-07-15 /pmc/articles/PMC8474257/ /pubmed/34589955 http://dx.doi.org/10.1016/j.jtocrr.2020.100074 Text en © 2020 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Ricciuti, Biagio
Naqash, Abdul Rafeh
Naidoo, Jarushka
Sehgal, Kartik
Miller, Adam
Kehl, Kenneth
Venkatraman, Deepti
Sands, Jacob
Lamberti, Giuseppe
Recondo, Gonzalo
Zhang, Jiajia
Macherla, Shravanti
Baig, Sameer
Walker, Paul
Rangachari, Deepa
Gainor, Justin F.
Costa, Daniel B.
Rizvi, Naiyer
Sholl, Lynette M.
Nishino, Mizuki
Henick, Brian
Farago, Anna F.
Awad, Mark M.
Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC
title Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC
title_full Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC
title_fullStr Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC
title_full_unstemmed Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC
title_short Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC
title_sort association between immune-related adverse events and clinical outcomes to programmed cell death protein 1/programmed death-ligand 1 blockade in sclc
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474257/
https://www.ncbi.nlm.nih.gov/pubmed/34589955
http://dx.doi.org/10.1016/j.jtocrr.2020.100074
work_keys_str_mv AT ricciutibiagio associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT naqashabdulrafeh associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT naidoojarushka associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT sehgalkartik associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT milleradam associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT kehlkenneth associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT venkatramandeepti associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT sandsjacob associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT lambertigiuseppe associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT recondogonzalo associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT zhangjiajia associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT macherlashravanti associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT baigsameer associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT walkerpaul associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT rangacharideepa associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT gainorjustinf associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT costadanielb associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT rizvinaiyer associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT sholllynettem associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT nishinomizuki associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT henickbrian associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT faragoannaf associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc
AT awadmarkm associationbetweenimmunerelatedadverseeventsandclinicaloutcomestoprogrammedcelldeathprotein1programmeddeathligand1blockadeinsclc