Association between past medical history (PMH) of autoimmune events and adverse events of special interest (AESI).

Abstract

2565 Background: PD-1/L1 inhibitor therapy has become the standard of care for many advanced solid tumors. A notable limitation of PD-1/L1 inhibitor therapy is the concern for AESI that are likely to be immune related. It is unclear whether a history of autoimmune events is a predisposing risk making these adverse events more likely. We aimed to evaluate the association between autoimmune-associated PMH and AESI on PD-1/L1 inhibitors. Methods: We pooled data across seven pivotal trials for PD-1/L1 inhibitors in urothelial cancer (UC) identifying patients with AESI submitted from 2016 - 2017. AESI were determined using a pooled preferred term list for each trial. Information collected from trials included PMH, AESI events and toxicity grade. Results: In total, 1747 immunotherapy treated patients were identified, with 1068 (61%) having an AESI and 277 (26%) having an autoimmune-related PMH. The most common autoimmune-associated events in the PMH were thyroid disorders (64%), asthma (23%), atopic dermatitis/eczema (6%), irritable bowel syndrome (5%), and psoriasis (4%). AESI occurred in 68% of patients with an autoimmune-related PMH and 60% of patients without an autoimmune-related PMH. The most common AESI in patients with an autoimmune-related PMH were diarrhea (35%), rash (27%), renal disorder (27%), and pruritis (23%). The most common AESI in the general trial population were diarrhea (28%), pruritis (26%), rash (25%), increased creatinine (14%), and elevated AST and ALT (10% and 9%). The majority of events were Grade 1-2 (87% in patients with an autoimmune-related PMH and 84% in the general trial population). Conclusions: Pooled clinical trial data shows a slight numeric increase in AESIs in patients with autoimmune-associated PMH. Limitations include potential lack of consistency of PMH documentation and adverse event reporting. There did not appear to be a pattern of association between PMH and type of AESI event. Grades of AESI events in the population with autoimmune-associated PMH were similar to the general trial population. This suggests that PD-1/L1 inhibitors may be safely administered to patients with UC and a PMH of some autoimmune-associated events. Further exploration is needed.