**4. Immune checkpoints inhibitors toxicity**

As reported by the current clinical trials, treatment-related AEs were very common in patients undergoing anti-PD-1 treatment (**Table 1**). However, grade 3 or above treatment-related AEs were generally only observed in less than 30% of patients. Here, we use the studies with most patients enrolled as examples (i.e., *n* = 243 for Armand et al. [36] and *n* = 210 for Chen et al. [40]). As reported by Armand et al. [36], the most common treatment-related AEs of any grade were fatigue (23%),

diarrhea (15%), and infusion-related reactions (14%). However, none of them were severe (grade 3 or above). On contrary, the most common grade 3 or 4 treatmentrelated AEs were lipase increases (5%), neutropenia (3%), and ALT increases. The most common treatment-related AEs that led to treatment discontinuation were pneumonitis (2%) and autoimmune hepatitis (1%). Other serious treatment-relate AEs included infusion-related reactions (2%), pneumonia (1%), pleural effusion (1%), and pyrexia (1%). For the study conducted by Chen et al. [40], the most common treatment-related AEs were hypothyroidism (14.3%), pyrexia (11.4%), rash (11.0%), and fatigue (11.0%). The most common grade 3 or 4 treatment-relate AEs were neutropenia (2.4%) and diarrhea (1.4%). Fourteen patients discontinued treatment due to treatment-related AEs, and the most common causes were pneumonitis in seven (3.3%) and infusion-related reactions in two (1.0%). Here, we will briefly discuss some cases that deserve special attention.
