Toxicities of single agent and combination immune checkpoint inhibitors in patients with autoimmune diseases.

Abstract

e14176 Background: Autoimmunity is associated with increased risk of malignancy. However, patients with pre-existing autoimmune diseases (AIDs) have been excluded from trials of immune checkpoint inhibitors (ICIs) known to cause immune activation and lead to immune related adverse events (irAEs). Data is limited on the safety and efficacy of these agents when used in AID patients and physicians are therefore wary to use them in this at-risk population. Methods: We conducted a single institution retrospective study to evaluate the safety and efficacy of ICI therapy in patients with pre-existing AIDs from 2011 to 2018. Primary endpoints were irAEs and AID flares. The secondary endpoint was overall survival (OS). Results: Of 84 total patients, 70 (83%) received ICI monotherapy and 14 (17%) received combination therapy. AIDs included: rheumatic 40 (48%), dermatologic 25 (30%), endocrine 16 (19%) and gastrointestinal 14 (17%) diseases of which 18 (21%) were on immune suppression. Combination therapy was associated with higher rates of severe grade 3-4 irAEs in 5/14 (36%) patients versus 8/70 (11%) with monotherapy (p = 0.022). ICIs were discontinued due to irAEs in 10/84 (12%) of all patients; 4/14 (29%) in the combination group and 6/70 (9%) in the monotherapy group (p = 0.057). While 32 patients (38%) had at least one AID flare, ICI was only permanently discontinued in 2 patients. Flare rates were higher for combination use: 8/14 (57%) compared to 23/70 (33%) for monotherapy (p = 0.086). Combination therapy was associated with higher median OS 27.8 months [95% CI 11.4-44.3] compared to monotherapy 12.3 months [95% CI 9.7-14.8] (p = 0.0007). OS had a positive correlation with flare (p = 0.007) and severe irAEs (p = 0.037). Conclusions: Our data suggest that rates of irAEs in patients with pre-existing AIDs are similar to those reported in the literature with single agent ICIs. While risk of severe irAEs and flares is increased with combination therapy, they are associated with overall survival. In our cohort, irAEs and flares were manageable and in most patients did not require permanent discontinuation for monotherapy or combination therapy suggesting that ICIs should be offered to this population, albeit with caution.