Emma L Mitchell1, Peter Kar Han Lau2, Chloe Khoo2, David Liew3, Jessica Leung1, Bonnia Liu4, Adam Rischin5, Albert G Frauman6, Damien Kee2, Kortnye Smith2, Benjamin Brady7, Danny Rischin8, Andrew Gibson9, Linda Mileshkin8, Oliver Klein10, Andrew Weickhardt10, Surein Arulananda10, Mark Shackleton5, Grant McArthur8, Andrew Östör9, Jonathan Cebon11, Benjamin Solomon8, Russell Rc Buchanan12, Ian P Wicks13, Serigne Lo14, Rodney J Hicks15, Shahneen Sandhu16. 1. Department of Rheumatology, Royal Melbourne Hospital, Australia; Department of Rheumatology, Austin Health, Melbourne, Australia. 2. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. 3. Department of Rheumatology, Austin Health, Melbourne, Australia; Department of Clinical Pharmacology and Therapeutics, Austin Health, Melbourne, Australia; Department of Medicine, University of Melbourne, Australia. 4. Department of Rheumatology, Austin Health, Melbourne, Australia. 5. Alfred Hospital, Melbourne, Australia. 6. Department of Clinical Pharmacology and Therapeutics, Austin Health, Melbourne, Australia; Department of Medicine, University of Melbourne, Australia. 7. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Cabrini Health, Melbourne, Australia. 8. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department, University of Melbourne, Melbourne, Australia. 9. Cabrini Health, Melbourne, Australia. 10. Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia. 11. Department of Medicine, University of Melbourne, Australia; Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia. 12. Department of Rheumatology, Austin Health, Melbourne, Australia; Department of Medicine, University of Melbourne, Australia. 13. Department of Rheumatology, Royal Melbourne Hospital, Australia; Walter and Eliza Hall Institute, Melbourne, Australia. 14. Melanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia; Institute for Research and Medical Consultations, University of Dammam, Dammam, Saudi Arabia. 15. Sir Peter MacCallum Department, University of Melbourne, Melbourne, Australia. 16. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department, University of Melbourne, Melbourne, Australia. Electronic address: shahneen.sandhu@petermac.org.
Abstract
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. Crown
IMPORTANCE: Rheumatic immune-related adverse events (irAEs) occur in approximately 10-20% of anti-programmed death 1 (anti-PD1)-treated cancerpatients. 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-PD1tumour efficacy. METHODS:Cancerpatients 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 cancerpatients 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. Crown
Authors: William Murray-Brown; Tom D Wilsdon; Helen Weedon; Susanna Proudman; Shawgi Sukumaran; Sonja Klebe; Jennifer G Walker; Malcolm D Smith; Mihir D Wechalekar Journal: J Immunother Cancer Date: 2020-06 Impact factor: 13.751
Authors: Bart Vanhaesebroeck; Matthew W D Perry; Jennifer R Brown; Fabrice André; Klaus Okkenhaug Journal: Nat Rev Drug Discov Date: 2021-06-14 Impact factor: 112.288