Ipilimumab and early signs of pulmonary toxicity in patients with metastastic melanoma: a prospective observational study

Abstract

Ipilimumab, an immune checkpoint inhibitor, is approved for treatment metastastic melanoma and is a promising agent against other malignancies. There is some preliminary evidence from case reports that ipilimumab treatment may be associated with pulmonary side effects. However, data from prospective studies on ipilimumab-related pulmonary toxicity are still scarce. Serial spirometries and measurements of CO-diffusion capacity (DLCO) in patients with metastatic melanoma before and during treatment with ipilimumab were performed. A reduction from baseline of forced vital capacity (FVC) of ≥ 10%, or ≥ 15% of DLCO was defined as clinically meaningful and indicative for pulmonary toxicity. Of 71 patients included in this study, a clinically meaningful lung function decline was registered in 6/65 (9%), 5/44 (11%), and 9/38 (24%) patients after 3, 6, and 9 weeks of treatment initiation, respectively. Even after adjusting for age, concomitant melanoma treatment, progressive pulmonary metastases, and baseline pulmonary function values, mean ± SD DLCO decreased significantly during follow-up (-4.3% ± 13.6% from baseline, p = 0.033). Only 7% of patients reported respiratory symptoms. Clinically manifest ipilimumab-related pneumonitis was diagnosed only in one patient (1.4%). DLCO decline maybe an early indicator of subclinical pulmonary drug toxicity. Therefore, routine pulmonary function testing including DLCO measurement during treatment might help for risk stratification to screen for ipilimumab-related pneumonitis.

Tumor-conditional anti-CTLA4 uncouples antitumor efficacy from immunotherapy-related toxicity

“…In contrast, mice treated with anti-CTLA4 DVD had intact hepatic architecture, with only scarce amounts of lymphocytes present in the liver ( Figure 4B; liver section). Pulmonary toxicity has also been reported in patients receiving ipilimumab treatments (21,22). In our study, we also observed anti-CTLA4-mediated lung toxicities associated with perivascular and peribronchial lymphocyte aggregates leading to bronchiolitis and pneumonitis.…”

Pneumonitis Induced by Immune Checkpoint Inhibitors: From Clinical Data to Translational Investigation

“…Bronchoalveolar lavage (BAL) can be used in the differential diagnosis, often manifested by an increase in the proportion of lymphocytes. In addition, a prospective observational study suggested that lung function tests during treatment might be helpful for risk stratification to screen for CIP (36). Usually, a bronchoscopic biopsy is not considered, but it can be used when it is difficult to make a differential diagnosis (37).…”

Pulmonary complications of immune checkpoint inhibitors in patients with nonsmall cell lung cancer

“…Moreover, eight out of 16 patients and nine out of 12 patients in the NAIDOO et al [76] series had, initially, a lowered forced expiratory volume in 1 s and diffusing capacity of the lung for carbon monoxide (D LCO ), respectively. Otherwise, FRANZEN et al [84] prospectively followed 71 patients with melanoma treated using ipilimumab, using pulmonary function tests. These authors reported a significant decrease in forced vital capacity (FVC) (>10%) or D LCO (>15%) after 9 weeks observed in nine (24%) out of 38 patients, with one of the patients presenting with pneumonitis in a thoracic CT scan.…”