Rheumatic immune-related adverse events secondary to anti-programmed death-1 antibodies and preliminary analysis on the impact of corticosteroids on anti-tumour response: A case series
- Mitchell, EL; Lau, PKH; Khoo, C; Liew, D; Leung, J; Liu, B; Rischin, A; FRAUMAN, AG; Kee, D; Smith, K; Brady, B; Rischin, D; Gibson, A; Mileshkin, L; Klein, O; Weickhardt, A; Arulananda, S; Shackleton, M; McArthur, G; Ostor, A; Cebon, J; Solomon, B; Buchanan, RR; Wicks, IP; Lo, S; Hicks, RJ; Sandhu, S;
- Journal Title
- European Journal of Cancer
- Publication Type
- Journal Article
- 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.
- WEHI Research Division(s)
- PubMed ID
- Publisher's Version
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2018-11-20 09:12:52Last Modified: 2018-11-20 01:06:09