Abstract
Objective We aimed to retrospectively analyze the predictors of immune checkpoint inhibitors (ICIs)-efficacy in patients with advanced pancancer who were treated with various ICIs in the real world and focused on the correlation between ICIs-efficacy and immune-related adverse events (irAEs). Methods We retrospectively analyzed data from 103 patients with advanced pancancer treated receiving various ICIs in the First Hospital of Jilin University from January 1, 2016 to August 1, 2020. Survival probabilities of progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier curves and log-rank tests and the multivariate Cox proportional hazards model. Receiver-operating characteristic curve was used to determine a cutoff value for parameters and area under the curve. Correlations between the two variables were analyzed by logistic regression. Results All patients were analyzed for survival predictors of OS, while 87 of 103 patients experienced evaluable disease progression of immunotherapy and were included in the analysis of predictors of PFS. First, we found that lower platelet (cutoff = 201.5 × 109/L) and lactate dehydrogenase (LDH) (cutoff = 227 U/L) were independently associated with significantly improved PFS, while lower platelet-lymphocyte ratio (cutoff = 206.5), absolute monocyte count (cutoff = 0.62 × 109/L), and LDH (cutoff = 194.5 U/L) were significantly and independently associated with better OS. In the analysis of the immune cell subgroup, a lower absolute countof CD8+CD28−suppressor T cells was an independent factor associated with better PFS (6.60 vs.4.13 months (mo), hazard ratios (HR) = 3.17, p = 0.0038), and OS (29.4 vs. 9.57 mo, HR = 3.05, p = 0.03). Second, the results of the analysis for irAEs showed that patients with any grade irAEs had higher objective response rate (30% vs. 10%, HR = 4.34, p = 0.009), disease control rate (69.7% vs. 50%, HR = 2.3, p = 0.028), PFS (8.37 vs. 3.77 mo, HR = 2.02, p = 0.0038), and OS (24.77 vs.13.83 mo, HR = 1.84, p = 0.024). Moreover, the groups with irAEs of grade ≥2 and with “multi-site” irAEs had significantly better PFS and OS (p < 0.05) compared with the other groups. We also proved that endocrine irAEs (usually thyroid dysfunction) were significantly associated with better mPFS (p = 0.01), and hepatic irAEs were significantly associated with better mOS (p = 0.023). Conclusions This retrospective study explored the availability and effectiveness of some cost-effective and readily available blood biochemical parameters in routine clinical practice to predict the ICIs-efficacy and demonstrated the predictive role of different categories of irAEs on efficacy.
Highlights
As a novel class of antitumor drugs, immune checkpoint inhibitors (ICIs) have shown durable and significant efficacy in the treatment of a variety of malignant tumors [1,2,3,4]
IrAEs assessed by patients every 4 weeks were recorded throughout the treatment, which are defined as adverse events (AEs) that are related to immunotherapeutic drugs during immunotherapy, and have a potential immunological basis, including the skin, endocrine, pulmonary, gastrointestinal, hepatic, neurological, hematological, and other rare AEs
Studies suggest that complete blood counts may be markers of cancer inflammation and adaptive immune response and that laboratory parameters in clinical routine have the advantages of convenience, practicality, and economy in predicting clinical outcomes of patients treated with ICIs. ose have been reported in some previous studies, for example, higher pretreatment RLC and REC in patients treated with pembrolizumab [15], lower absolute monocyte count (AMC) [16], higher AEC [16], higher absolute lymphocyte count (ALC) [17], lower RLC [16] at baseline, and increased ALC and AEC during treatment [18] were associated with favorable survival outcomes
Summary
As a novel class of antitumor drugs, immune checkpoint inhibitors (ICIs) have shown durable and significant efficacy in the treatment of a variety of malignant tumors [1,2,3,4]. Reliable laboratory parameters have not been established in daily clinical routine to predict the clinical outcome after treatment with ICIs, but some studies have shown that such convenient, practical, and cost-effective indicators may be helpful in selecting patients who may benefit, while guiding those with a low chance of alternative treatment. A number of recent studies have reported this view [11,12,13], data on the impact of irAEs on long-term survival outcomes in clinical practice are conflicting and have not been clarified Based on this, this retrospective study aimed to comprehensively analyze the convenient and available indicators that can predict the efficacy of ICIs in patients with advanced pancancer who were treated with multiple types of ICIs in the real world and focused on the correlation between ICIsefficacy and irAEs that are currently of great concern to clinicians and clinical outcomes
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