Background
Immune checkpoint inhibitors (ICIs) are now standard-of-care across several tumour types and in various disease settings. ICIs act by enhancing an immune response and thus associated with toxicity which mirrors autoimmunity yet possess a different natural history. Management of severe immune-related adverse events (irAE) is resource intensive, usually requiring additional specialty input – both limited in a regional setting.
Aim
To describe presentation and management of severe irAEs within regional setting.
Methods:
A retrospective cohort of regional Victorian patients (Latrobe Regional Hospital, Bairnsdale Regional Health Service, Central Gippsland Health) receiving at least one dose of ICI (pembrolizumab, nivolumab, ipilimumab, atezolizumab, cemiplimab, durvalumab, avelumab) between 1 July 2018 - 30 June 2021. Clinicopathlogical, cancer treatment, toxicity (as per CTCAE v5) and survival data was obtained. Statistical analysis performed using excel and R.
Results:
Total of 373 patients, with 232 (62%) male. Median age 69 years (IQR 63-75). Over 80% (313/373) were ECOG 0-1 and mean Charlson score 8.7. Eighty percent (302) had metastatic disease. 208/373 (55%) had lung cancer, followed by melanoma (25%), others <10%. Nivolumab was the most common ICI (65%), used in combination with ipilimumab in 2%. Pembrolizumab (32%), Atezolizumab (9%), Durvalumab (5%), Avelumab (<1%) and Cemiplimab (<1%) were also utilised. Severe toxicity (grade 3-5) requiring hospital admission occurred in 40/373 (11%). Four treatment-related deaths occurred. Treatment breaks followed all severe irAE. Nearly 50% were re-challenged. Rash (7%), colitis (6%), pneumonitis (3%), hepatitis (3%) most common. 32/373 (9%) required IV methylprednisolone and infliximab in 3. Tertiary centre transfer for irAE management occurred in 9%. There was no difference in overall survival between severe irAE and the total cohort (21.73 vs 22.9 months, p=0.2).
Conclusions:
Optimal management of ICI related severe irAE in a regional setting is achievable with contemporary protocols and responsive metropolitan support.