TY - JOUR
T1 - Rheumatic immune-related adverse events secondary to anti–programmed death-1 antibodies and preliminary analysis on the impact of corticosteroids on anti-tumour response
T2 - A case series
AU - Mitchell, Emma L.
AU - Lau, Peter Kar Han
AU - Khoo, Chloe
AU - Liew, David
AU - Leung, Jessica
AU - Liu, Bonnia
AU - Rischin, Adam
AU - Frauman, Albert G.
AU - Kee, Damien
AU - Smith, Kortnye
AU - Brady, Benjamin
AU - Rischin, Danny
AU - Gibson, Andrew
AU - Mileshkin, Linda
AU - Klein, Oliver
AU - Weickhardt, Andrew
AU - Arulananda, Surein
AU - Shackleton, Mark
AU - McArthur, Grant
AU - Östör, Andrew
AU - Cebon, Jonathan
AU - Solomon, Benjamin
AU - Buchanan, Russell RC
AU - Wicks, Ian P.
AU - Lo, Serigne
AU - Hicks, Rodney J.
AU - Sandhu, Shahneen
N1 - Funding Information:
Dr Mitchell has received travel support from Pfizer . Dr Lau has received travel support from Bristol-Myers Squibb ; honoraria from Bristol-Myers Squibb and Pfizer and receives a Australian Government Research Training Scholarship. Dr Khoo has received travel support from Roche . Dr Shackleton has received honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, Merck Serono and research funding from Bristol-Myers Squibb . Dr McArthur has been a consultant or advisor for Provectus; received research funding from Pfizer , Celgene and Ventana and has had travel accommodation and expenses paid for by Roche and Novartis. Dr Klein has received travel support from Bristol-Myers Squibb and honoraria for advisory board from Bristol-Myers Squibb and Merck. Dr Buchanan has received travel support from Bristol-Myers Squibb . Dr D. Rischin has been an uncompensated consultant for Amgen, Merck, Regeneron and received clinical trial research funding from Amgen , Bristol-Myers Squibb , Genentech , Merck and Regeneron . Dr Solomon has received honoraria for advisory boards from Bristol-Myers Squibb, Merck, Roche-Genentech, AstraZeneca, Pfizer and Novartis. Dr Hicks has been an uncompensated advisory board member for Novartis, Ipsen and Telix Pharmaceuticals. Dr Sandhu has received honoraria for advisory board from Bristol-Myers Squibb, Merck, Merck Serano, Janssen; uncompensated advisory boards for AstraZeneca and Genetech and research funding from Amgen , Pfizer and Tolmar . No relevant disclosures were noted for doctors Liew, Leung, Liu, A. Rischin, Frauman, Kee, Smith, Brady, Gibson, Mileshkin, Weickhardt, Arulananda, Östör, Cebon, Wicks, and Lo.
Funding Information:
Dr Mitchell has received travel support from Pfizer. Dr Lau has received travel support from Bristol-Myers Squibb; honoraria from Bristol-Myers Squibb and Pfizer and receives a Australian Government Research Training Scholarship. Dr Khoo has received travel support from Roche. Dr Shackleton has received honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, Merck Serono and research funding from Bristol-Myers Squibb. Dr McArthur has been a consultant or advisor for Provectus; received research funding from Pfizer, Celgene and Ventana and has had travel accommodation and expenses paid for by Roche and Novartis. Dr Klein has received travel support from Bristol-Myers Squibb and honoraria for advisory board from Bristol-Myers Squibb and Merck. Dr Buchanan has received travel support from Bristol-Myers Squibb. Dr D. Rischin has been an uncompensated consultant for Amgen, Merck, Regeneron and received clinical trial research funding from Amgen, Bristol-Myers Squibb, Genentech, Merck and Regeneron. Dr Solomon has received honoraria for advisory boards from Bristol-Myers Squibb, Merck, Roche-Genentech, AstraZeneca, Pfizer and Novartis. Dr Hicks has been an uncompensated advisory board member for Novartis, Ipsen and Telix Pharmaceuticals. Dr Sandhu has received honoraria for advisory board from Bristol-Myers Squibb, Merck, Merck Serano, Janssen; uncompensated advisory boards for AstraZeneca and Genetech and research funding from Amgen, Pfizer and Tolmar. No relevant disclosures were noted for doctors Liew, Leung, Liu, A. Rischin, Frauman, Kee, Smith, Brady, Gibson, Mileshkin, Weickhardt, Arulananda, Östör, Cebon, Wicks, and Lo.
Publisher Copyright:
© 2018
PY - 2018/12
Y1 - 2018/12
N2 - Importance: Rheumatic immune-related adverse events (irAEs) occur in approximately 10–20% of anti–programmed death 1 (anti-PD1)–treated cancer patients. There are limited data on the natural history, optimal treatment and long-term oncological outcomes of patients with rheumatic irAEs. Objective: The objective of the study was to describe the spectrum and natural history of rheumatic irAEs and the potential impact of rheumatic irAEs and immunomodulators on anti-PD1 tumour efficacy. Methods: Cancer patients with pre-existing rheumatic disease before anti-PD1 therapy or de novo rheumatic irAEs on anti-PD1 therapy were retrospectively reviewed across three sites. Patient demographics, treatment history, anti-PD1 irAEs, and anti-PD1 responses were evaluated. Relationships between the development or pre-existence of rheumatic irAE, use of immunomodulatory agents and outcomes were evaluated. Results: This multicenter case series describes 36 cancer patients who had rheumatic disease before anti-PD1 therapy (n = 12) or developed de novo rheumatic irAEs (n = 24). Thirty-four of the 36 patients sustained rheumatic irAEs (median time to rheumatic irAE: 14.5 weeks), including 24 de novo (18 inflammatory arthritis, three myositis, two polymyalgia rheumatica, one fasciitis) and 10 flares in 12 patients with pre-existing rheumatic disease. Corticosteroids were used in 30 of 36 patients (median duration: 10 months), and disease-modifying antirheumatic drugs were used in 14 of 36 patients (median duration: 5.5 months). The objective response rate to anti-PD1 therapy was 69% (n = 25/36) overall and 81% (n = 21/26) in the melanoma subgroup. Conclusions: Rheumatic irAEs are often chronic and require prolonged immunomodulatory therapy. Prospective studies are required to define optimal management of rheumatic irAEs that maintain long-term anticancer outcomes.
AB - Importance: Rheumatic immune-related adverse events (irAEs) occur in approximately 10–20% of anti–programmed death 1 (anti-PD1)–treated cancer patients. There are limited data on the natural history, optimal treatment and long-term oncological outcomes of patients with rheumatic irAEs. Objective: The objective of the study was to describe the spectrum and natural history of rheumatic irAEs and the potential impact of rheumatic irAEs and immunomodulators on anti-PD1 tumour efficacy. Methods: Cancer patients with pre-existing rheumatic disease before anti-PD1 therapy or de novo rheumatic irAEs on anti-PD1 therapy were retrospectively reviewed across three sites. Patient demographics, treatment history, anti-PD1 irAEs, and anti-PD1 responses were evaluated. Relationships between the development or pre-existence of rheumatic irAE, use of immunomodulatory agents and outcomes were evaluated. Results: This multicenter case series describes 36 cancer patients who had rheumatic disease before anti-PD1 therapy (n = 12) or developed de novo rheumatic irAEs (n = 24). Thirty-four of the 36 patients sustained rheumatic irAEs (median time to rheumatic irAE: 14.5 weeks), including 24 de novo (18 inflammatory arthritis, three myositis, two polymyalgia rheumatica, one fasciitis) and 10 flares in 12 patients with pre-existing rheumatic disease. Corticosteroids were used in 30 of 36 patients (median duration: 10 months), and disease-modifying antirheumatic drugs were used in 14 of 36 patients (median duration: 5.5 months). The objective response rate to anti-PD1 therapy was 69% (n = 25/36) overall and 81% (n = 21/26) in the melanoma subgroup. Conclusions: Rheumatic irAEs are often chronic and require prolonged immunomodulatory therapy. Prospective studies are required to define optimal management of rheumatic irAEs that maintain long-term anticancer outcomes.
KW - Anti–programmed death 1 antibodies
KW - Arthritis
KW - Corticosteroid
KW - Disease-modifying antirheumatic drug
KW - Immune checkpoint inhibitor
KW - Immune-related adverse event
KW - Melanoma
KW - Myositis
KW - Polymyalgia rheumatica
KW - Rheumatic irAE
UR - http://www.scopus.com/inward/record.url?scp=85056543413&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2018.09.027
DO - 10.1016/j.ejca.2018.09.027
M3 - Article
C2 - 30439628
AN - SCOPUS:85056543413
VL - 105
SP - 88
EP - 102
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
ER -
