- This retrospective study, the first of its kind, evaluated clinical and radiologic outcomes of 41 patients with preexisting computed tomography (CT) evidence of interstitial lung disease (ILD) who received pembrolizumab or nivolumab for lung cancer (73%) or another malignancy
- There were 23 deaths over the one-year follow-up period; patients died more frequently from cancer progression (n=16, 70%) or other non-ILD causes (n=4, 17%) than from hypoxemic respiratory failure attributable to ILD (n=3, 13%)
- Three patients (7%) developed PD-1 inhibitor–related pneumonitis
- When considering a PD-1 inhibitor for a cancer patient with ILD, the risk of pneumonitis must be considered but should be weighed against the potential for life-extending treatment
The limited clinical literature available suggests patients with interstitial lung disease (ILD) who are treated with a programmed cell death–1 (PD-1) inhibitor are at increased risk of immune-related pneumonitis. Accordingly, such patients have been excluded from some cancer trials of PD-1 inhibitors. There is also concern that PD-1 inhibitors and other immunotherapies may worsen underlying ILD.
Subscribe to the latest updates from Pulmonary & Critical Care Advances in Motion
To address the knowledge gap, Sydney B. Montesi, MD, and Amita Sharma, MBBS, clinician-researchers in the Divisions of Pulmonary and Critical Care and Thoracic Imaging and Intervention at Massachusetts General Hospital, and colleagues reviewed clinical and radiologic outcomes in 41 patients with preexisting computed tomography (CT)evidence of ILD who were treated with pembrolizumab or nivolumab at Mass General between September 1, 2014, and June 30, 2018. The primary cancer types were lung (73%) and head and neck (12%).
In their report in Clinical Lung Cancer, the researchers conclude it is unnecessary to routinely withhold PD-1 inhibitors from patients with ILD.
- 17 patients (42%) were alive at the end of the one-year follow-up period, one (2%) had been lost to follow-up and 23 (56%) had died
- Three deaths (13%) were attributed to hypoxemic respiratory failure from ILD. These three patients had a usual interstitial pneumonia (UIP)pattern of ILD
- 16 deaths (70%) were attributed to cancer progression and four (17%) to other causes
11 patients were hospitalized for respiratory-related causes. Three of these hospitalizations (7%), all in patients with primary lung cancer, were related to ILD and were attributed to pneumonitis (two related to PD-1 inhibitors and one to docetaxel).
One additional patient developed PD-1 inhibitor-related pneumonitis but was not hospitalized, for a total of three patients with PD-1 inhibitor–related pneumonitis (7%).
63.4% of patients had stable ILD findings on follow-up CT, 12.2% had improved findings, 22.0% showed progression and 2.4% had mixed results.
Guidance for Physicians
When considering a PD-1 inhibitor for cancer treatment in a patient with ILD, the risk–benefit analysis should be tailored to the individual patient. The risk of pneumonitis must be considered but should be weighed against the potential for life-extending treatment.
CT follow-up times were highly variable in this study (17–419 days) and the duration of anti–PD-1 therapy also varied. Therefore, the results should be interpreted with caution and should not be used to infer a potential effect of PD-1 inhibitor therapy on underlying ILD.
Neither should the results be extrapolated to judge the safety of using other immune checkpoint inhibitors in patients with ILD, or the safety of PD-1 inhibitors for patients with concurrent autoimmune disease.
Refer a patient to the Division of Pulmonary and Critical Care Medicine