Yuzo Suzuki1, Masato Karayama2, Tomohiro Uto3, Masato Fujii4, Takashi Matsui5, Kazuhiro Asada6, Hideki Kusagaya7, Masato Kato8, Hiroyuki Matsuda9, Shun Matsuura10, Mikio Toyoshima11, Kazutaka Mori12, Yasuhiro Ito13, Takafumi Koyauchi2, Hideki Yasui2, Hironao Hozumi2, Kazuki Furuhashi2, Noriyuki Enomoto2, Tomoyuki Fujisawa2, Yutaro Nakamura2, Naoki Inui2, Takafumi Suda2. 1. Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: yuzosuzu@hama-med.ac.jp. 2. Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. 3. Department of Respiratory Medicine, Iwata City Hospital, Iwata, Japan. 4. Department of Respiratory Medicine, Shizuoka City Shizuoka Hospital, Shizuoka, Japan. 5. Department of Respiratory Medicine, Seirei-Mikatahara Hospital, Hamamatsu, Japan. 6. Department of Respiratory Medicine, Shizuoka General Hospital, Shizuoka, Japan. 7. Department of Respiratory Medicine, Shizuoka Saiseikai Hospital, Shizuoka, Japan. 8. Department of Respiratory Medicine, JA Shizuoka Kohseiren Enshu Hospital, Hamamatsu, Japan. 9. Department of Respiratory Medicine, Shizuoka Red Cross Hospital, Shizuoka, Japan. 10. Department of Respiratory Medicine, Fujieda City Hospital, Fujieda, Japan. 11. Department of Respiratory Medicine, Hamamatsu Rosai Hospital, Hamamatsu, Japan. 12. Department of Respiratory Medicine, Shizuoka City Shimizu Hospital, Shizuoka, Japan. 13. Department of Respiratory Medicine, Tenryu Hospital, National Hospital Organization, Hamamatsu, Japan.
Abstract
INTRODUCTION: Programmed cell death protein 1 immune checkpoint inhibitors (ICIs) have been reported to improve the survival of patients with NSCLC. On the expansion of clinical administration for a variety of cancers, immune-related adverse events have been typically recognized to be associated with ICIs, therefore, necessitating the monitoring and management of these patients. Among immune-related adverse events, immune-related interstitial lung disease (ir-ILD) is a serious complication that interrupts treatment and can occasionally be fatal. However, no prospective studies have investigated the incidence of ir-ILD and associated risk factors for its development in the clinical setting. METHODS: This is a prospective cohort study consisting of patients with NSCLC treated with ICIs. Baseline characteristics, including laboratory data, pulmonary function tests, daily symptoms of dyspnea defined by the modified Medical Research Council, and antitumor response were assessed. RESULTS: Among the 138 patients with NSCLC who received anti-programmed cell death protein 1 monotherapy, 20 patients (14.5%) had ir-ILD within median 51.5 days (interquartile range: 29-147). This was approximately three times higher than those in clinical trials. A total of 11 patients (55.0%), including all eight patients with high-grade ir-ILD (≥grade 3), developed ir-ILD within 60 days. Impaired spirometry, decreased forced vital capacity and forced expiratory volume in 1 second, and daily symptoms of dyspnea measured using the modified Medical Research Council scale were identified as risk factors for ir-ILD development. In addition, combination assessment of forced vital capacity and forced expiratory volume in 1 second successfully classified patients at risk for ir-ILD development. CONCLUSIONS: The incidence of ir-ILD was substantially higher in the clinical setting. Assessment of spirometry and daily dyspneic symptoms before ICI treatment may be useful in monitoring and managing patients with NSCLC.
INTRODUCTION: Programmed cell death protein 1 immune checkpoint inhibitors (ICIs) have been reported to improve the survival of patients with NSCLC. On the expansion of clinical administration for a variety of cancers, immune-related adverse events have been typically recognized to be associated with ICIs, therefore, necessitating the monitoring and management of these patients. Among immune-related adverse events, immune-related interstitial lung disease (ir-ILD) is a serious complication that interrupts treatment and can occasionally be fatal. However, no prospective studies have investigated the incidence of ir-ILD and associated risk factors for its development in the clinical setting. METHODS: This is a prospective cohort study consisting of patients with NSCLC treated with ICIs. Baseline characteristics, including laboratory data, pulmonary function tests, daily symptoms of dyspnea defined by the modified Medical Research Council, and antitumor response were assessed. RESULTS: Among the 138 patients with NSCLC who received anti-programmed cell death protein 1 monotherapy, 20 patients (14.5%) had ir-ILD within median 51.5 days (interquartile range: 29-147). This was approximately three times higher than those in clinical trials. A total of 11 patients (55.0%), including all eight patients with high-grade ir-ILD (≥grade 3), developed ir-ILD within 60 days. Impaired spirometry, decreased forced vital capacity and forced expiratory volume in 1 second, and daily symptoms of dyspnea measured using the modified Medical Research Council scale were identified as risk factors for ir-ILD development. In addition, combination assessment of forced vital capacity and forced expiratory volume in 1 second successfully classified patients at risk for ir-ILD development. CONCLUSIONS: The incidence of ir-ILD was substantially higher in the clinical setting. Assessment of spirometry and daily dyspneic symptoms before ICI treatment may be useful in monitoring and managing patients with NSCLC.
Authors: James G Connolly; Megan Fiasconaro; Kay See Tan; Michael A Cirelli; Gregory D Jones; Raul Caso; Daniel E Mansour; Joseph Dycoco; Jae Seong No; Daniela Molena; James M Isbell; Bernard J Park; Matthew J Bott; David R Jones; Gaetano Rocco Journal: J Thorac Cardiovasc Surg Date: 2021-12-23 Impact factor: 6.439