Pre-existing PF Increases Risk of Lung Inflammation Among Lung Cancer Patients Using Opdivo or Keytruda, Study Suggests

Pulmonary fibrosis significantly increases the risk of severe pneumonitis (inflammation of lung tissue)  among patients with lung cancer who were treated with Opdivo or Keytruda, a retrospective study suggests.

The study “Pre-existing pulmonary fibrosis is a risk factor for anti-PD-1-related pneumonitis in patients with non-small cell lung cancer: A retrospective analysis” was published in the journal Lung Cancer.

Bristol-Myers Squibb’s Opdivo (nivolumab) and Merck’s Keytruda (pembrolizumab) are two programmed death-1 (PD-1) immune checkpoint inhibitors designed to harness the immune system in order to help restore an anti-tumor immune response. Checkpoint inhibitors are commonly hijacked by cancer cells to halt the immune system’s response against tumors.

Opdivo and Keytruda are both approved therapies for certain patients with advanced non-small cell lung cancer (NSCLC).

However, increasing evidence shows that patients treated with either of these therapies may develop potentially life-threatening immune disorders, including pneumonitis; the rate of pneumonitis affects 3 to 5% of NSCLC patients treated with Opdivo or Keytruda.

Interstitial lung disease (ILD) is a risk factor for pneumonitis, but because patients with ILD usually are excluded from clinical trials, it remains unknown whether ILD, including pulmonary fibrosis, is linked with the development of pneumonitis in Opdivo or Keytruda-treated patients.

So, researchers investigated the potential link between pulmonary fibrosis and pneumonitis in patients with NSCLC who were treated with Opdivo or Keytruda. They also looked at the link between emphysema, a condition characterized by damaged alveoli (the lung’s air sacs), and pneumonitis in these patients.

The team performed a retrospective analysis of data from 123 NSCLC patients (median age 68 years), treated with Opdivo or Keytruda at the Aichi Cancer Center Hospital in Japan, between December 2015 and November 2017. Chest computed tomography was used to evaluate patients’ fibrosis severity (scores from 0 to 5) and emphysema (scores from 0 to 4).

Results showed that 18 patients (14.6%) experienced treatment-related pneumonitis, of which four (3.3%) scored 3 or higher in terms of severity. The median number of days after starting anti-PD-1 therapy for patients to develop pneumonitis was 60 days (range from six to 634 days).

All pneumonitis cases were resolved, expect for a single case graded 5 in severity. The median overall survival after the onset of pneumonitis was 18 months.

By analyzing the data according to the fibrosis score, researchers found that pneumonitis occurred in 13 (35.1%) of the 37 patients with a fibrosis score of one or higher, and in five (5.8%) of 86 patients with a fibrosis score of zero.

Regarding the emphysema score, pneumonitis occurred in 11 (22.9%) of 48 patients with an emphysema score of one or higher, and in seven (9.3%) of 75 patients with an emphysema score of zero. Patients with emphysema, but no fibrosis (18 patients), did not experience pneumonitis.

Overall, “our results indicate that pre-existing pulmonary fibrosis significantly increases the risk of anti-PD-1-related pneumonitis” in patients with NSCLC, researchers wrote, adding that “even mild pulmonary fibrosis might increase the risk of anti-PD-1-related pneumonitis.”

“Further studies are required, however, to explore the predictive factors of anti-PD-1-related pneumonitis in patients with both NSCLC and ILD,” the team concluded.