Patterns and outcomes of immune-related adverse events in solid tumor patients treated with immune checkpoint inhibitors in Thailand: a multicenter analysis

Abstract

Background Most immune-related adverse event (irAE) patterns and treatment guidelines are based on western clinical data. We evaluated the incidence and patterns of irAEs in patients treated with immune-checkpoint inhibitors (ICI) in Thailand. Methods All solid tumor patients treated with ICIs were retrospectively reviewed in a multicenter analysis. The study aims to evaluate the incidence of irAEs and their characteristics, treatments, outcomes, and impact on survival. All irAEs were graded using the CTCAE version 4.0. Characteristics of irAEs including time to onset, duration of irAEs, specific treatments, and outcomes of irAEs were reviewed. The Chi-square or Fisher’s exact test was used to compare variables. Overall survival (OS) was estimated by the Kaplan-Meier method, and compared by the log-rank test. A p-value < 0.05 was considered statistically significant. Results irAEs of any grade were observed in 98 of 414 patients (24%), whereas grades 3–4 irAEs were observed in 5.6%. The majority of patients (78%) were treated with monotherapy ICI (anti-PD1/PD-L1 92%). The most common all-grade irAEs were hypothyroidism (7.5%), hepatitis (6.5%), and rash (4.8%). Median onset of overall irAEs was 63 days. Pancreatitis and pneumonitis had the earliest onset at 30 and 34 days, respectively. ICIs were rechallenged in 68 of 98 patients with irAE. Eleven of sixty-eight patients (11.2%) with initial irAE had reoccurrence after ICI rechallenge. Based on a multivariate analysis, pre-existing hypothyroidism, ICI used in a clinical trial setting, and combinations of ICI/ICI were independent factors predicting irAE occurrence. Patients with irAE had a statistically significant longer overall survival (OS) when compared to patients without irAE (p = 0.019). A multivariate analysis revealed that occurrence of irAE was an independent prognostic factor for OS (HR 0.70, 95% CI 0.51–0.96; p = 0.028). Conclusion irAE was commonly observed in Thai cancer patients treated with ICIs. Most irAEs were low-grade and manageable. Re-occurrence of irAE after re-challenging ICI was not uncommonly observed. Patients who experienced irAEs might have significantly longer OS compared to patients without irAEs. However, OS in this study should be interpreted with caution since it might be affected by various tumor types, treatment settings, dosing schedule, and ICI combinations.

Immune‐related adverse events and outcomes among pan‐cancer patients receiving immune checkpoint inhibitors: A monocentric real‐world observational study

“…The relationships of irAEs onset and prognosis have been studied previously. [12][13][14] In line with previous studies, we found that patients with irAEs onset would achieve better prognosis than patients without irAEs, in the aspect of PFS and OS. Furthermore, we demonstrated that onset of skin toxicities would indicate a better PFS, which is also consistent with other studies.…”

“…The relationships of irAEs onset and prognosis have been studied previously 12–14 . In line with previous studies, we found that patients with irAEs onset would achieve better prognosis than patients without irAEs, in the aspect of PFS and OS.…”

“…IrAEs can occur during therapy or even several months after ICI cessation, although they most often present early after ICI treatment 11 . Interestingly, the occurrence of irAEs may predict patients' prognosis 12–14 . Therefore, monitoring and timely handling irAEs are of critical importance.…”

Immune‐related adverse events in urothelial cancer patients: Adjustment for immortal time bias

“…Although our landmark analysis did not fully resolve the immortal bias, by excluding patients with survival periods shorter than 3 months in the present study, this underling bias was reduced, thereby strengthening our findings. Three months seemed to be long enough as the setting of landmark because the median time of onset of overall irAEs is about 2 months, and majority of irAEs appears within 3 months, as previously reported 22,23 . The results were similar when the analysis was limited to patients who survived more than 6 months.…”

“…Three months seemed to be long enough as the setting of landmark because the median time of onset of overall irAEs is about 2 months, and majority of irAEs appears within 3 months, as previously reported. 22,23 The results were similar when the analysis was limited to patients who survived more than 6 months. To further emphasize the significance of irAEs as a predictor of efficacy to pembrolizumab, a sensitivity analysis was also performed.…”