Analysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events

Abstract

Objective: We aimed to retrospectively analyze the toxicity profiles and predictors of immune-related adverse events (irAEs) as well as the correlation between irAEs and the clinical efficacy of multi-type immune checkpoint inhibitors (ICIs) in patients with advanced pan-cancer in a real-world setting. Methods: We retrospectively analyzed data from 105 patients with advanced pan-cancer treated with multi-type ICIs at the First Hospital of Jilin University between January 1, 2016 and August 1, 2020. We used logistic regression analyses to investigate the associations of irAEs with clinical baseline characteristics, blood count parameters, and biochemical indicators during treatment. Receiver operating characteristic curves were used to determine cutoff values for parameters and area under the curve values. Kaplan–Meier and Cox multivariate regression analyses were performed to estimate the relationships of baseline characteristics and irAEs with progression-free survival (PFS) and overall survival (OS). Results: A lower relative lymphocyte count (cutoff = 28.5%), higher albumin level (cutoff = 39.05 g/L), and higher absolute eosinophil count (AEC) (cutoff = 0.175 × 109/L) were significantly associated with the occurrence of irAEs, among which a higher AEC (cutoff = 0.205 × 109/L) was strongly associated with skin-related irAEs [odds ratios (ORs) = 0.163, P = 0.004]. Moreover, a higher lactate dehydrogenase level (cutoff = 237.5 U/L) was an independent predictor of irAEs of grade ≥ 3 (OR = 0.083, P = 0.023). In immune cell subgroup analysis, a lower absolute count of CD8+CD28− suppressor T cells (OR = 0.806; 95% confidence interval: 0.643–1.011; P = 0.062), which are regulatory T lymphocytes, was associated with the occurrence of irAEs, although the difference was not statistically significant. Furthermore, a higher percentage of CD19+ B cells was associated with the occurrence of irAEs of grade ≥ 3 (P = 0.02) and grade ≥ 2 (P = 0.051). In addition, patients with any grade of irAE had a significantly high PFS (8.37 vs. 3.77 months, hazard ratios (HR) = 2.02, P = 0.0038) and OS (24.77 vs. 13.83 months, HR = 1.84; P = 0.024). Conclusions: This retrospective study reports clinical profile data for irAEs in unselected patients in a real-world setting and explored some parameters that may be potential predictive markers of the occurrence, type, or grade of irAEs in clinical practice. Evidence of a correlation between safety and efficacy may facilitate a complete assessment of the risk-benefit ratio for patients treated with ICIs.

Blood cell counts can predict adverse events of immune checkpoint inhibitors: A systematic review and meta-analysis

“…The types of blood counts reported are as follows: absolute eosinophil count (AEC), derived neutrophil: lymphocyte ratio (dNLR), neutrophil: lymphocyte ratio (NLR), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute monocyte count (AMC), platelet count (PLT), monocyte: lymphocyte ratio (MLR), platelet: lymphocyte ratio (PLR), etc. Eight studies showed substantial truncation values ( 11 , 15 – 17 , 20 , 23 , 25 , 28 ). Eleven studies reported the use of receiver operating characteristic (ROC) curve analysis to calculate the optimal cutoff value ( 11 , 15 – 17 , 19 – 21 , 23 – 26 ).…”

“…Eight studies showed substantial truncation values ( 11 , 15 – 17 , 20 , 23 , 25 , 28 ). Eleven studies reported the use of receiver operating characteristic (ROC) curve analysis to calculate the optimal cutoff value ( 11 , 15 – 17 , 19 – 21 , 23 – 26 ). In all included reports, skin adverse reactions were the most common (23.34%), followed by endocrine adverse reactions (22.81%), immune pneumonia (13.50%), hepatic adverse reactions (10.25%), and gastrointestinal adverse reactions (9.23%).…”

Cutaneous Adverse Reactions of Immunotherapy in Patients with Advanced Melanoma

“…It has been reported that patients with preexisting autoimmune diseases are at an increased risk of experiencing flare-ups following ICB administration [ 11 ]. Similarly, personal and familial histories of psoriasis are significant predictors of psoriasis development following ICB treatment [ 12 ].…”

PD-1 inhibitors provide new opportunities in conversion therapy for stage IV gastric cancer

“…The most common immune-associated adverse events (AEs) were of grade 1-2: 8 patients had skin responses, 2 of which were of grade 3 or 4, and all others were of grade 1 or 2, with rash being the most common AE; 3 patients had endocrine AEs (mainly hypothroidism/hyperthroidism), and one patient had grade 4 hemorrhage, which might have been associated with apatinib. Some parameters that may be potential predictive biomarkers of immune-associated AEs in clinical practice, especially when immune checkpoint inhibitors are combined with chemotherapy and or targeted drugs 21 .…”