Association Between Immune-Related Adverse Events and Efficacy and Changes in the Relative Eosinophil Count Among Patients with Advanced Urothelial Carcinoma Treated by Pembrolizumab

Abstract

Background To evaluate the association between immune-related adverse events (irAEs) and the clinical outcomes and also between irAEs and the post-treatment changes in the relative eosinophil count (REC) in advanced urothelial carcinoma (UC) patients treated with pembrolizumab. Materials and Methods This retrospective study analyzed 105 advanced UC patients treated with pembrolizumab after disease progression on platinum-based chemotherapy between January 2018 and June 2021. The association between the occurrence of irAEs and the efficacy of pembrolizumab was investigated. The change in the REC from before the initiation of pembrolizumab therapy, to three weeks after treatment and the incidence of irAEs were determined. Results Overall irAEs were associated with a significantly higher objective response rate (ORR) (58.8% vs 25.4%, P<0.001), a longer progression-free survival (PFS) (25.1 months vs 3.1 months, P< 0.001) and overall survival (OS) (31.2 months vs 11.5 months, P< 0.001) compared to patients without irAEs; however, grade ≥3 irAEs were not associated with the ORR (36.4% vs 36.2%, P=0.989), PFS (9.5 vs 5.5 months, P=0.249), or OS (not reached vs 13.7 months, P=0.335). Compared to a decreased REC at 3 weeks after pembrolizumab, an increased relative REC at 3 weeks was not associated with the incidence of any-grade irAEs (32.3% vs 32.5%, P=0.984) or of grade ≥3 irAEs (10.8% vs 10.0%, P=0.900). Multivariate analyses revealed a female sex (P=0.005), Eastern Cooperative Oncology Group Performance Status ≥1 (P=0.024), albumin <3.7 g/dl (P<0.001), decreased REC (3 weeks later) (P<0.001), and the absence of irAEs of any grade (P=0.002) to be independently associated with a worse OS. Conclusion Patients with irAEs showed a significantly better survival compared to patients without irAEs in advanced UC treated with pembrolizumab. An increased posttreatment REC may be a marker predicting improved clinical outcomes and it had no significant relationship with the incidence of irAEs.

Eosinophil may be a predictor of immune‐related adverse events induced by different immune checkpoint inhibitor types: A retrospective multidisciplinary study

“…[17][18][19][20] Although the detailed underlying mechanisms about association between eosinophils and irAEs occurrence are unclear, previous studies supported our data that increased eosinophils may reflect efficacy and safety in patients treated with ICIs. 16,18,[24][25][26][27]38 In the past, most studies have shown that ICImediated irAEs may be associated with an improved response to therapy and survival outcomes in several types of cancers. [43][44][45][46] Consistently, our data revealed significantly longer mOS and mPFS in patients with irAEs than in those without irAEs, as reported in another study (Figure 4A,B).…”

PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with BRPC/LAPC: A biomolecular exploratory, phase II trial

“…Notably, a positive association between eosinophil invasion of tumor tissue or an increase in PBEC and superior response to ICIs in several types of cancer has been reported. 20 , 37 Although the underlying mechanism is not fully understood, there is strong evidence that eosinophils exhibit antitumor effects. Thus, eosinophils affect the immune response to diseases such as cancer, and predictive biomarkers that reflect this inflammatory response to treatment may be useful for clinical decision-making in the management of patients with cancer.…”

The Eosinophil Changes, Efficacy and Safety of Pembrolizumab in Advanced Urothelial Carcinoma Patients with an Older Age and a Poor Performance Status

“…Several studies, including studies on advanced UC, have reported a possible association between the incidence of irAEs and the clinical efficacy of ICIs. [28][29][30] In the PS ≥2 group, the shorter OS may have been due to the lower incidence of irAEs. In addition, interestingly, patients with PS ≥2 did not show a change of eosinophils, increase of REC, and decrease NER, while these values showed significant changes in patients with PS 0-1.…”