Clinical Outcomes of Patients with Advanced Cancer and Pre-Existing Autoimmune Diseases Treated with Anti-Programmed Death-1 Immunotherapy: A Real-World Transverse Study

Abstract

Background Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors. Materials and Methods Consecutive patients with advanced cancer, treated with anti‐programmed death‐1 (PD‐1) agents, were evaluated according to the presence of pre‐existing AIDs. The incidence of immune‐related adverse events (irAEs) and clinical outcomes were compared among subgroups. Results A total of 751 patients were enrolled; median age was 69 years. Primary tumors were as follows: non‐small cell lung cancer, 492 (65.5%); melanoma, 159 (21.2%); kidney cancer, 94 (12.5%); and others, 6 (0.8%). Male/female ratio was 499/252. Eighty‐five patients (11.3%) had pre‐existing AIDs, further differentiated in clinically active (17.6%) and inactive (82.4%). Among patients with pre‐existing AIDs, incidence of irAEs of any grade was significantly higher when compared with patients without AIDs (65.9% vs. 39.9%). At multivariate analysis, both inactive (p = .0005) and active pre‐existing AIDs (p = .0162), female sex (p = .0004), and Eastern Cooperative Oncology Group Performance Status <2 (p = .0030) were significantly related to a higher incidence of irAEs of any grade. No significant differences were observed regarding grade 3/4 irAEs and objective response rate among subgroups. Pre‐existing AIDs were not significantly related with progression‐free survival and overall survival. Conclusion This study quantifies the increased risk of developing irAEs in patients with pre‐existing AIDs who had to be treated with anti‐PD‐1 immunotherapy. Nevertheless, the incidence of grade 3/4 irAEs is not significantly higher when compared with control population. The finding of a greater incidence of irAEs among female patients ranks among the “hot topics” in gender‐related differences in immuno‐oncology. Implications for Practice Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors but are frequent in clinical practice. This study quantifies the increased risk of developing immune‐related adverse events (irAEs) in patients with pre‐existing AIDs who had to be treated with anti‐programmed death‐1 immunotherapy. Nevertheless, their toxicities are mild and the incidence of grade 3/4 irAEs is not significantly higher compared with those of controls. These results will help clinicians in everyday practice, improving their ability to offer a proper counselling to patients, in order to offer an immunotherapy treatment even to patients with pre‐existing autoimmune disease.

Late immune-related adverse events in long-term responders to PD-1/PD-L1 checkpoint inhibitors: a multicentre study

“…By definition, long-responders are positively selected patients; being able to be treated for a long time, with typically a lower tumor burden and fit to receive ICIs. In our study population, only Globally, our study confirms the spectrum of all-grade irAEs described in both clinical trials and real-life studies with PD-1/PD-L1 inhibitors [22][23][24]; cutaneous (19.3%), endocrine (13.9%), and GI (10.8%) irAEs were the most commonly reported. Although they were not among the most frequent, rheumatologic irAEs had an incidence of 9.9%, higher than previously described in literature (0.7-5.1%) [24][25].…”

To treat or not to treat: Patient exclusion in immune oncology clinical trials due to preexisting autoimmune disease

“…31 Overall, 47.1% of the patients with AD experienced an AD flare, 65.9% experienced an irAE, and 9.4% developed a grade 3/4 irAE. Underlying AD was associated with an increased risk of irAEs.…”

“…Similarly, a large retrospective study of 751 patients treated with anti-PD-1 agents at 15 Italian centers between 2013 and 2018 compared safety and efficacy outcomes for subjects with (n = 85) and without preexisting AD (n = 666). 31 Overall, 47.1% of the patients with AD experienced an AD flare, 65.9% experienced an irAE, and 9.4% developed a grade 3/4 irAE. The authors found that although patients with AD were more likely to develop an irAE of any grade, they were not more likely to develop a grade 3/4 irAE.…”

Autoimmune complications of immunotherapy: pathophysiology and management

“…In a prospective registry study, patients with an underlying autoimmune disease (n=45) had a shorter time to irAE onset than those without (n=359), median 5.4 months versus 13 months (P=2.1×10 −4 ) 49. A prospective observational study of 751 cancer patients (85 with an autoimmune disease) treated with anti-PD1 showed that irAEs were more common in patients with an underlying autoimmune disease than in those without, 66%, (50 to 86) versus 40% (35 to 45) but that high grade irAEs occurred with similar frequencies, 9.4% (4.1 to 19) versus 8.8% (6.7 to 11.4)50 (in that study, no relationship was seen between the presence of an autoimmune disease and progression free or overall survival). In a retrospective cohort study of 102 patients with pre-existing inflammatory bowel disease treated with ICIs, 41% experienced gastrointestinal adverse events compared with 11% in patients without inflammatory bowel disease (odds ratio, 3.61; 95% confidence interval 0.85 to 15.27; P=0.081), but the incidence of de novo irAEs was not reported 51.…”