Study Examines Incidence, Risk Factors for ICI-Related Pneumonitis in NSCLC

Immune checkpoint inhibitor (ICI)-related pneumonitis occurs at a high rate among patients with advanced non–small cell lung cancer (NSCLC) and increases the risk of mortality, new findings of a single-center study show.

Furthermore, data revealed interstitial lung disease increased the risk for pneumonitis, especially in never-smokers. Results were published in The Oncologist.

Although the use of ICIs in NSCLC has led to gains in life expectancy, the activation of T cells that results from ICI treatment can increase the risk of immune-related adverse events (irAEs).

“In contrast to the well-characterized temporal patterns of classic chemotherapy toxicities, such as alopecia, nausea/vomiting, and myelosuppression, the onset and duration of irAEs are unpredictable, and predisposing factors for individuals to develop irAEs remain unclear,” researchers explained.

Pneumonitis, which is characterized by lung inflammation, is the most common cause of treatment-related mortality. Previous studies show that risk factors for the condition vary. To better examine predisposing risk factors and incidence of pneumonitis in those with NSCLC undergoing treatment with ICIs, the investigators conducted a retrospective review of 419 patients.

All individuals had advanced NSCLC and were treated with anti–PD-L1 monoclonal antibodies given as a monotherapy or in combination with an anti–CTLA-4-blocking therapy between 2013 and 2021. The researchers gleaned clinical, imaging, and microbiological data from patients’ electronic health records.

Forty patients (9.5%) had pneumonitis during the study window. The median (IQR) time from start date of treatment with ICI to pneumonitis was 215 (120-330) days (range, 6-879) after ICI initiation, the authors noted.

Analyses revealed:

• Thirty-five patients had grade 2 (n = 21) or grade 3 (n = 14) pneumonitis, while 5 patients died due to pneumonitis
• Pneumonitis increased the risk for mortality (HR, 1.6; 95% CI, 1.0-2.5), after adjustment for disease progression (HR, 1.6; 95% CI, 1.4-1.8) and baseline shortness of breath (HR, 1.5; 95% CI, 1.2-2.0)
• Incomplete resolution was more common with more severe pneumonitis
• Interstitial lung disease was associated with higher risk for pneumonitis (HR, 5.4; 95% CI, 1.1-26.6), particularly in never-smokers (HR, 26.9; 95% CI, 2.8-259.0)

Patients had a median age of 64 at enrollment, and 74% were former smokers. More than 80% of patients were also treated with first-line immunotherapy and less than 5% received a concurrent anti–CTLA-4 agent. Nearly 60% of patients had preexisting chronic obstructive pulmonary disease.

Of the 361 individuals who stopped ICI treatment, reasons included:

• Death: 20.5%
• Pneumonitis: 15.4%
• Non-lung irAEs: 32.9%
• Non-irAE toxicities: 42.12%
• Disease progression: 232.64%

The study revealed a higher rate of pneumonitis than that reported in initial clinical trials, the authors said. This could be due to the longer follow-up times in the current study. They suggested strategies for monitoring the condition should account for it occurring well after the start of ICI treatment.

“Our cohort had a large preexisting burden of lung disease, and our data suggest that risk factors for pneumonitis may vary by smoking history,” they explained. “While interstitial lung disease, particularly in never-smokers, was associated with a higher risk for pneumonitis, prior lung disease was not otherwise associated with mortality. Following pneumonitis, nearly half of patients had residual scarring.”

The study was carried out in a single center, and findings may not be generalizable. In addition, it is limited to patients with NSCLC alone.

“Our work highlights that detailed pretreatment characterization of lung disease may improve our ability to identify patients at high risk for pneumonitis,” the authors concluded.

Reference:

Altan M, Soto F, Zhong LL, et al. Incidence and risk factors for pneumonitis associated with checkpoint inhibitors in advanced non-small cell lung cancer: a single center experience. Oncologist. Published online May 8, 2023. doi:10.1093/oncolo/oyad118