Safety and efficacy of immunotherapy rechallenge following checkpoint inhibitor-related pneumonitis in advanced lung cancer patients: a retrospective multi-center cohort study.

Checkpoint inhibitor-related pneumonitis (CIP) immune checkpoint inhibitors (ICIs) lung cancer rechallenge

Journal

Translational lung cancer research
ISSN: 2218-6751
Titre abrégé: Transl Lung Cancer Res
Pays: China
ID NLM: 101646875

Informations de publication

Date de publication:
Nov 2022
Historique:
received: 19 07 2022
accepted: 08 11 2022
entrez: 15 12 2022
pubmed: 16 12 2022
medline: 16 12 2022
Statut: ppublish

Résumé

Checkpoint inhibitor-related pneumonitis (CIP) induced by immune checkpoint inhibitors (ICIs) is one of the most fatal immune-related adverse events (irAE). However, only limited data are available on rechallenge with ICIs after CIP. We evaluated the efficacy and safety of rechallenge after CIP in patients with advanced lung cancer to identify the potential populations that would benefit. We conducted a multicenter retrospective study of advanced lung cancer patients who received further ICI treatment (rechallenge) or did not undergo re-administration after grade ≥1 CIP between May 2017 and May 2021. Progression-free survival (PFS) and overall survival (OS) were estimated from first or second ICI initiation to disease progression (PFS1 and PFS2, respectively), death, or last follow-up (OS1 and OS2, respectively). The recurrence of CIP and new irAEs in these patients after ICI rechallenge were calculated. Among 107 patients afflicted with CIP, 45 (42.1%) received ICI rechallenge. Multivariate analysis showed that severe grade (grades ≥3) and ground-glass opacity of pneumonitis lesions were negatively associated with rechallenge. Following rechallenge, 9 (20.0%) patients developed recurrent pneumonitis, and 11 (24.4%) developed a new irAE. Severe grade of CIP and poor performance status at initial CIP as well as levels of interleukin (IL)-6 and C-reactive protein (CRP), and absolute white blood cell and neutrophil counts at the time of ICI rechallenge were associated with a higher recurrence rate. The median (95% confidence interval) PFS1 and PFS2 were 17.9 (9.9-24.2) and 15.5 (5.5-25.6) months, respectively. The median (95% confidence interval) OS1 and OS2 were 23.5 (16.5-30.5) and 18.4 (10.1-26.7) months, respectively. Lower OS2 was observed in patients with severe grade of CIP and poor performance status at the initial CIP, recurrence of CIP, and in patients with high levels of CRP and IL-6 at rechallenge. Only IL-6 was found to affect OS2 on multivariate analysis. ICI rechallenge following CIP may be a promising treatment for patients with advanced lung cancer, particularly in those with low-grade of CIP and good performance status at initial CIP, and low levels of IL-6 and CRP at the time of initial challenge. Prospective studies are needed for further verification.

Sections du résumé

Background UNASSIGNED
Checkpoint inhibitor-related pneumonitis (CIP) induced by immune checkpoint inhibitors (ICIs) is one of the most fatal immune-related adverse events (irAE). However, only limited data are available on rechallenge with ICIs after CIP. We evaluated the efficacy and safety of rechallenge after CIP in patients with advanced lung cancer to identify the potential populations that would benefit.
Methods UNASSIGNED
We conducted a multicenter retrospective study of advanced lung cancer patients who received further ICI treatment (rechallenge) or did not undergo re-administration after grade ≥1 CIP between May 2017 and May 2021. Progression-free survival (PFS) and overall survival (OS) were estimated from first or second ICI initiation to disease progression (PFS1 and PFS2, respectively), death, or last follow-up (OS1 and OS2, respectively). The recurrence of CIP and new irAEs in these patients after ICI rechallenge were calculated.
Results UNASSIGNED
Among 107 patients afflicted with CIP, 45 (42.1%) received ICI rechallenge. Multivariate analysis showed that severe grade (grades ≥3) and ground-glass opacity of pneumonitis lesions were negatively associated with rechallenge. Following rechallenge, 9 (20.0%) patients developed recurrent pneumonitis, and 11 (24.4%) developed a new irAE. Severe grade of CIP and poor performance status at initial CIP as well as levels of interleukin (IL)-6 and C-reactive protein (CRP), and absolute white blood cell and neutrophil counts at the time of ICI rechallenge were associated with a higher recurrence rate. The median (95% confidence interval) PFS1 and PFS2 were 17.9 (9.9-24.2) and 15.5 (5.5-25.6) months, respectively. The median (95% confidence interval) OS1 and OS2 were 23.5 (16.5-30.5) and 18.4 (10.1-26.7) months, respectively. Lower OS2 was observed in patients with severe grade of CIP and poor performance status at the initial CIP, recurrence of CIP, and in patients with high levels of CRP and IL-6 at rechallenge. Only IL-6 was found to affect OS2 on multivariate analysis.
Conclusions UNASSIGNED
ICI rechallenge following CIP may be a promising treatment for patients with advanced lung cancer, particularly in those with low-grade of CIP and good performance status at initial CIP, and low levels of IL-6 and CRP at the time of initial challenge. Prospective studies are needed for further verification.

Identifiants

DOI: 10.21037/tlcr-22-732 PMID: 36519018 PMC: PMC9742619
pubmed: 36519018
doi: 10.21037/tlcr-22-732
pii: tlcr-11-11-2289
pmc: PMC9742619
doi:

Types de publication

Journal Article

Langues

eng

Pagination

2289-2305

Informations de copyright

2022 Translational Lung Cancer Research. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-732/coif). YS serves as an unpaid editorial board member of Translational Lung Cancer Research from September 2020 to August 2022. MJ received lecturer fees, aboard fees and travel grants from AstraZeneca, Roche, Pfizer, Novartis, Takeda, MSD, Boehringeringelheim. The other authors have no conflicts of interest to declare.

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Auteurs

Xinqing Lin (X)

State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Haiyi Deng (H)

State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Tianqing Chu (T)

Department of Respiratory Medicine, Shanghai Chest Hospital, Jiaotong University, Shanghai, China.

Likun Chen (L)

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Yilin Yang (Y)

State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Guihuan Qiu (G)

State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Xiaohong Xie (X)

State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Yinyin Qin (Y)

State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Ming Liu (M)

State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Zhanhong Xie (Z)

State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Ming Ouyang (M)

State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Shiyue Li (S)

State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Yong Song (Y)

Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing, China.

Francesco Petrella (F)

Division of Thoracic Surgery, IRCCS European Institute of Oncology, Milan, Italy.
Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy.

Marko Jakopovic (M)

Department for Respiratory Diseases Jordanovac, University Hospital Centre, Zagreb, Croatia.
School of Medicine, University of Zagreb, Zagreb, Croatia.

Nikolaos Tsoukalas (N)

Department of Oncology, 401 General Military Hospital, Athens, Greece.

Piergiorgio Solli (P)

Department of Cardio-Thoracic Surgery and Hearth & Lung Transplantation, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Taichiro Goto (T)

Lung Cancer and Respiratory Disease Center, Yamanashi Central Hospital, Yamanashi, Japan.

Yuichi Saito (Y)

Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan.

Chengzhi Zhou (C)

State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Classifications MeSH