To investigate the relationship between radiotherapy (RT), in particular chest RT, and development of immune-related (IR) pneumonitis in non-small-cell lung cancer (NSCLC) patients treated with anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1).
Pneumonitis is a potential consequence of both lung-directed radiation and immune checkpoint blockade (ICB), particularly treatment with PD-1/PD-L1 inhibitors.
We performed a systematic review and network meta-analysis to compare the risk of immune-related pneumonitis among different PD1/PD-L1 inhibitor-related therapeutic regimens.
PD-1/PD-L1 inhibitor therapy for advanced NSCLC has a significantly higher ORR and a higher rate of immune-mediated pneumonitis when used in the first-line setting compared with chemotherapy treated patients.
The spectrum differed widely between regimens: in a total of 193 anti-CTLA-4 deaths, most were usually from colitis (135 [70%]), whereas anti-PD-1/PD-L1-related fatalities were often from pneumonitis (333 [35%]), hepatitis (115 [22%]), and neurotoxic effects (50 [15%]).
Patients treated with PD-1 inhibitors were found to have a slightly increased rate of immune-related AEs (16% [95% CI, 14%-17%] vs 11% [95% CI, 10%-13%]; P = .07) and pneumonitis (4% [95% CI, 3%-5%] vs 2% [95% CI, 1%-3%]; P = .01) compared with patients who received PD-L1 inhibitors.
Although many clinical trial results of PD-1/PD-L1 inhibitors had been reported incidence of pneumonitis, the knowledge based on the individual cohort data from each clinical trial is limited.
Herein we discuss two patients who developed pneumonitis secondary to anti-PD-1/PD-L1 immune checkpoint inhibitor therapy and illustrate a stepwise approach to the diagnostic evaluation and management of anti-PD-1/PD-L1-related pneumonitis.
Although several antibodies developed to target programmed cell death-1 (PD-1) and its ligand (PD-L1) have demonstrated great promise for the treatment of non-small cell lung cancer (NSCLC), and other malignancies, these therapeutic antibodies can cause pneumonitis.
High PD-L1 expression by immunohistochemistry staining was seen in intra-alveolar macrophages and viable tumor cells in the pneumonitis and recurrent tumor specimens, respectively.
Incidence of all-grade pneumonitis in PD-1 and PD-L1 inhibitor therapy (n=1,313) was significantly higher than that in chemotherapy (n=918) (OR=2.35, 95% CI, 1.32-4.20, P=0.004), but had no significance in grade 3-5 pneumonitis.
To address its biological relevance in vivo, we investigated the effect of corticosteroid plus LABA on the expression of PD-L1 in double-stranded RNA-induced lung inflammation in mice.
Importantly, the interaction of PD-1 with its ligand PD-L1 is vital to restrict the pro-inflammatory activities of lung effector T cells in situ, thereby inhibiting the development of excessive pulmonary inflammation and injury during RSV infection.