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 Academic Article uri icon

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.

authors

  • 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, Andrew
  • Arulananda, Surein
  • Shackleton, M
  • McArthur, G
  • Östör, A
  • Cebon, Jonathan
  • Solomon, B
  • Buchanan, RR
  • Wicks, IP
  • Lo, S
  • Hicks, RJ
  • Sandhu, S

publication date

  • 2018