Interleukin-6 blockade for prophylaxis and management of immune-related adverse events in cancer immunotherapy.
Adult
Aged
Antibodies, Monoclonal, Humanized
/ administration & dosage
Autoimmune Diseases
/ complications
C-Reactive Protein
/ analysis
Drug-Related Side Effects and Adverse Reactions
/ blood
Female
Humans
Immune Checkpoint Inhibitors
/ adverse effects
Interleukin-6
/ antagonists & inhibitors
Male
Melanoma
/ complications
Middle Aged
Prospective Studies
Retrospective Studies
Skin Neoplasms
/ complications
Symptom Flare Up
Immune-related adverse events
Immunotherapy
Inflammatory reaction
Tocilizumab
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
21
04
2021
revised:
15
08
2021
accepted:
18
08
2021
pubmed:
19
9
2021
medline:
15
12
2021
entrez:
18
9
2021
Statut:
ppublish
Résumé
Immune checkpoint inhibitors (ICIs) have activity across many tumor types, but activation of the immune system may also lead to significant, often steroid-refractory immune-related adverse events (irAEs). We sought to determine the activity of tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, in treatment or prevention of auto-immune irAE in ICI-treated patients. Institutional databases from 2 melanoma centers were reviewed for patients treated with ICIs and tocilizumab. Longitudinal assessment of C-reactive protein (CRP) and assessment of clinical improvement or prevention of flare of pre-existing auto-immune conditions were utilised to evaluate the benefit of tocilizumab. Twenty-two patients were identified. Two were treated prophylactically. Twenty were treated for management of irAEs. Median time to irAE onset from ICI start was 48 days (range 8-786) and from irAE onset to tocilizumab 32 days (range 1-192). Median time to irAE resolution from tocilizumab was 6.5 days (range 1-93). Clinical improvement/benefit was demonstrated in 21/22 patients. Median CRP prior to ICI administration was 32 mg/l (range 0.3-99), at the onset of irAE 49.5 mg/L (range 0.3-251, P = 0.047) and after tocilizumab 18 mg/L (range 0.3-18, P = 0.0011). Tocilizumab was well tolerated with self-limiting and transient toxicities in 11 (50%) patients. From start of ICI, median progression-free survival was 6 months (range 3.9-18.8) and median overall survival was not reached. Tocilizumab was a well-tolerated and effective steroid-sparing treatment for both management of irAEs, as well as prevention of flare of pre-existing auto-immune disorders. Prospective trials to evaluate its efficacy and impact on cancer outcomes compared with standard strategies are required.
Sections du résumé
BACKGROUND
Immune checkpoint inhibitors (ICIs) have activity across many tumor types, but activation of the immune system may also lead to significant, often steroid-refractory immune-related adverse events (irAEs). We sought to determine the activity of tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, in treatment or prevention of auto-immune irAE in ICI-treated patients.
METHODS
Institutional databases from 2 melanoma centers were reviewed for patients treated with ICIs and tocilizumab. Longitudinal assessment of C-reactive protein (CRP) and assessment of clinical improvement or prevention of flare of pre-existing auto-immune conditions were utilised to evaluate the benefit of tocilizumab.
RESULTS
Twenty-two patients were identified. Two were treated prophylactically. Twenty were treated for management of irAEs. Median time to irAE onset from ICI start was 48 days (range 8-786) and from irAE onset to tocilizumab 32 days (range 1-192). Median time to irAE resolution from tocilizumab was 6.5 days (range 1-93). Clinical improvement/benefit was demonstrated in 21/22 patients. Median CRP prior to ICI administration was 32 mg/l (range 0.3-99), at the onset of irAE 49.5 mg/L (range 0.3-251, P = 0.047) and after tocilizumab 18 mg/L (range 0.3-18, P = 0.0011). Tocilizumab was well tolerated with self-limiting and transient toxicities in 11 (50%) patients. From start of ICI, median progression-free survival was 6 months (range 3.9-18.8) and median overall survival was not reached.
CONCLUSIONS
Tocilizumab was a well-tolerated and effective steroid-sparing treatment for both management of irAEs, as well as prevention of flare of pre-existing auto-immune disorders. Prospective trials to evaluate its efficacy and impact on cancer outcomes compared with standard strategies are required.
Identifiants
pubmed: 34536945
pii: S0959-8049(21)00558-X
doi: 10.1016/j.ejca.2021.08.031
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
IL6 protein, human
0
Immune Checkpoint Inhibitors
0
Interleukin-6
0
C-Reactive Protein
9007-41-4
tocilizumab
I031V2H011
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
214-224Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.