Author: Olsson-Brown A.C.; Baxter M.; Dobeson C.; Feeney L.; Lee R.; Maynard A.; Mirza S.; Mughal S.; Parikh S.; Rodgers L.J.; Salawu A.; Shotton R.; Tinsley N.; Zhao S.S.; Jones C.
Abstract: Background: Immune-related adverse events (irAE) are a recognised complication of immune checkpoint inhibitor (ICI) therapy. Previous characterisation of irAEs has been limited to clinical trial or registry populations and small case series. Here we present a multi-centre, granular, real-world analysis of the prevalence and outcomes of irAEs experienced by patients managed within a single comprehensive public health service. Method(s): A multi-centre retrospective analysis of 2125 consecutive patients treated with ICIs was undertaken across 12 centres. All patients were managed within the UK National Health Service outside of a trial setting between June 2016 and September 2018. Patients received either ICI monotherapy (MT) or combination therapy (CT). Data were collected using a standardised, prepiloted, collection tool. IrAEs >= grade 2 or endocrinopathies of any grade were considered clinically significant and recorded as per the Common Terminology Criteria for Adverse Events (V5) (CTCAE). Descriptive statistics were employed using Stata v15 (College Station, TX). Result(s): Patients received alphaPD-1 (1757; 82%), combination alphaPD-1/alphaCTLA-4 (285, 13%), alphaCTLA-4 (51; 2%) and alphaPD-L1 (31; 1%) immunotherapy for malignant melanoma (961), non-small cell lung cancer (788) or renal cell carcinoma (335). The median age was 66 (MT) and 57 (CT). Clinically significant irAEs occurred in 732 (34%) individuals; 28% (524) on MT and 73% (208) on CT. Colitis (206,10%), thyroiditis (194, 9%), hepatitis (142, 7%) and dermatitis (126, 6%) were most commonly observed. Grade 1 endocrinopathies occurred in 20% (173) of cases. Grade 2 irAEs occurred in 43% (359), grade 3 31% (269) and grade 4 6% (51). The were 3 (0.4%) cases of grade 5 irAE; pneumonitis (2) and hepatitis, all following alphaPD-1 MT. 93% (680) required corticosteroids with 64% (490) requiring systemic corticosteroids and 11% (80) steroid sparing immunosuppression. 16% (336) of patients had pre-existing autoimmune disease of whom 40% (136) experienced irAEs. IrAEs led to admission in 42% (308) of cases, accounting for 2996 bed days. Length of stay was 7 days (1-67; IQR 4-13). Higher dependency care was required in 0.7% (15) of cases. Colitis (35%, 107) and hepatitis (25%, 77) accounted for the most admissions. Pneumonitis accounted for 3% (66) of irAEs but 12% of admissions. Conclusion(s): One third of patients experienced a clinically-significant irAE resulting in significant morbidity and admission burden highlighting the need for effective management strategies to optimise patient outcomes.
