Real World Study Of Immune Related Adverse Events Caused By PD-1 Inhibitors And Efficacy Correlation

Background: PD-1 inhibitors can often have unexpected anti-tumor effects by activating autoimmune tolerance.It is one of the most popular immune checkpoint inhibitors today bringing new therapeutic approaches to a variety of malignancies,especially in lung cancer.However,over-activated autoimmune by PD-1 inhibitors responses can lead to immune-related adverse events(ir AEs).Immune-related adverse events can show the damage of various systems,which is more specific than chemotherapy.When it damages important organs,it may cause irreparable consequences,or even death.Therefore,it is necessary to focus on the potential ir AEs in patients on PD-1 inhibitors in daily clinical practice.Methods: This study retrospectively studied the case data of 288 patients with solid tumors who applied PD-1 inhibitors attending Zhejiang Provincial People’s Hospital from 2019.04.01 to 2021.04.30.We analyzed the multiple aspects data of ir AEs,such as the incidence,time,spectrum and efficacy correlation of it.In parallel,we further explored the efficacy of PD-1 inhibitors for the lung cancer subgroup.Result: For 288 patients in our study,187 patients had no baseline measurement,69 patients had incomplete baseline measurement,and only 32 patients had comprehensive baseline measurement,accounting for 64.93%,23.95% and 11.11% respectively.The total incidence of ir AEs was 35.07%,and the incidence rate of grade I-II and III-V ir AEs were 30.38% and 4.69% respectively,one patient died of immune-related pneumonia,and the incidence of fatal ir AEs was 0.35%.Among 143 patients with lung cancer,the incidence of all grade ir AEs,III-V grade ir AEs and fatal ir AEs were 36.36%,3.50% and0.70% respectively.Hypothyroidism is the most common ir AEs,followed by liver function injury,followed by skin reaction,weakness and immune pneumonia.The median onset time of ir AEs was 3.15 months(mean time was 4.09 M,95CI [3.43,4.74]).The median time of grade I-II ir AEs and III-IV ir AEs was 3.20 months.There was no statistically significant difference between the above two groups(P = 0.1460).Among the 14 patients with grade III-V ir AEs,only 4 patients received hormone replacement therapy,and continued PD-1 inhibitor after ir AEs degradation.Compared with patients without ir AEs,patients with ir AEs had longer OS and PFS(m OS: 10.80 vs 6.32 months,P=0.0102;m PFS: 8.95 vs 4.73 months,P<0.0001).Patients with earlier ir AEs had significantly improved OS and PFS(m OS: 13.51 vs 8.24 months,P=0.0007;m PFS:11.29 vs 6.74 months,P=0.0012)than later ir AEs,but high-level ir AEs didn’t mean a better prognosis.There was no significant difference in the incidence of ir AEs among tumor species.In SCLC,lung adenocarcinoma and lung squamous cell carcinoma,PD-1inhibitors showed a trend of better survival benefit in first-line treatment compared with later-line(P values of OS are 0.1099,0.0502 and 0.0470 respectively;P values of PFS are0.0104,0.0098 and 0.0333 respectively).In the first-line treatment of lung adenocarcinoma and lung squamous cell carcinoma,PD-1 inhibitors combined with chemotherapy and antiangiogenics show a better combined effect(P values of OS are0.0168 and 0.0939 respectively;P values of PFS are 0.0478 and 0.0261 respectively).Conclusion: Complete baseline measurements are required before treatment with PD-1inhibitors to prevent the occurrence of ir AEs.ir AEs mostly occurred about 3.15 months(6 cycles)after PD-1 inhibitors treatment.The ir AEs was not related to the type of tumor.The presence and onset time of ir AEs tends to predict the efficacy of PD-1 inhibitors.However,the presence of high-grade ir AEs doesn’t indicate better outcomes.For patients with high-level ir AEs,them should be standardized treat according to the guidelines and hormones and even immunosuppressants should be used in sufficient quantities in time.In lung cancer patients,PD-1 inhibitors combine with antiangiogenics and chemotherapy maybe have a synergistic effect.We suggest that PD-1 inhibitors could be applied in first-line treatment of lung cancer if possible.