Safety of immune check-point inhibitors in patients with autoimmune conditions and advanced cancer

Abstract

Background: Immune check-point inhibitors (ICI) have revolutionised the treatment of advanced cancer. However, ICI treatment is associated with immune related adverse events (irAEs) leading to patient morbidity and mortality. Safety and efficacy of ICI is not well known in patients with auto-immune (AI) conditions as historically this group has been excluded from clinical trials. The aim of our study was to evaluate the safety and efficacy of primarily anti-PD1 therapy in patients with known AI conditions. Method(s): This was a retrospective analysis of patients with advanced cancer treated with ICI at 5 Australian hospitals. Result(s): 17 patients were identified: melanoma (11), NSCLC (5) and 1 with mRCC. AI conditions: Crohn's disease (1), Ulcerative colitis (3), rheumatoid arthritis (5 including 1 with common variable immune-deficiency), psoriasis (4) and 4 patients with other AI disease. Treatment received: Nivolumab (7 including 1 with prior Ipilimumab), Pembrolizumab (8) and Ipilimumab (2). 11 patients previously received systemic therapy for their AI condition, 2 had topical therapy and 4 had no previous therapy. Two patients had symptoms of active AI disease at time of starting ICI. Disease flared in 6/17 (35%): 3 with G2 arthritis (2 treated with moderate dose steroids, one with anti-inflammatories), G3 colitis treated with high dose steroids, G3 dyspnoea treated with high dose steroids and G2 psoriatic rash treated with low dose steroids. Nil required steroid sparing agents. irAEs unrelated to AI disease flare: 3 patients with pneumonitis, two G2, one G3 all requiring high dose steroids and one patient with G3 colitis requiring high dose steroids. Response rates: complete (1), partial (7), stable (2) progressive disease (5), non-evaluable (2). Conclusion(s): Disease flared in 35% of patients with AI conditions undergoing treatment with ICI. Most patients were successfully managed with steroids and treatment was permanently discontinued in only one patient. Although use of ICI in patients with AI conditions seems generally manageable, our data should be interpreted with caution as many patients with AI conditions had no symptoms of active disease at the start of therapy. Response to ICI is similar to historical controls.