Steroid-refractory PD-(L)1 pneumonitis: incidence, clinical features, treatment, and outcomes

• Published in: Journal for immunotherapy of cancer Vol. 9; no. 1; p. e001731
• Main Authors: Balaji, Aanika, Hsu, Melinda, Lin, Cheng Ting, Feliciano, Josephine, Marrone, Kristen, Brahmer, Julie R, Forde, Patrick M, Hann, Christine, Zheng, Lei, Lee, Valerie, Illei, Peter B, Danoff, Sonye K, Suresh, Karthik, Naidoo, Jarushka
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01-01-2021; BMJ Publishing Group
• Series: Original research
• Subjects: Adrenal Cortex Hormones - therapeutic use; Adult; Aged; Aged, 80 and over; Cancer; Cell death; Chemotherapy; Clinical/Translational Cancer Immunotherapy; Drug Resistance - drug effects; Fatalities; Female; Hospitalization; Humans; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Immunoglobulins; Immunoglobulins, Intravenous - administration & dosage; Immunoglobulins, Intravenous - therapeutic use; Immunotherapy; Incidence; Infliximab - administration & dosage; Intensive Care Units; Laboratories; Lung Neoplasms - drug therapy; Lung Neoplasms - epidemiology; Male; Middle Aged; Multidisciplinary teams; Outpatient care facilities; Patients; Pneumonia - drug therapy; Pneumonia - epidemiology; Radiation; Retrospective Studies; Survival Analysis; Ventilators; programmed cell death 1 receptor; inflammation; immunotherapy
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2020-001731

BackgroundImmune-checkpoint inhibitor (ICI)-pneumonitis that does not improve or resolve with corticosteroids and requires additional immunosuppression is termed steroid-refractory ICI-pneumonitis. Herein, we report the clinical features, management and outcomes for patients treated with intravenous immunoglobulin (IVIG), infliximab, or the combination of IVIG and infliximab for steroid-refractory ICI-pneumonitis.MethodsPatients with steroid-refractory ICI-pneumonitis were identified between January 2011 and January 2020 at a tertiary academic center. ICI-pneumonitis was defined as clinical or radiographic lung inflammation without an alternative diagnosis, confirmed by a multidisciplinary team. Steroid-refractory ICI-pneumonitis was defined as lack of clinical improvement after high-dose corticosteroids for 48 hours, necessitating additional immunosuppression. Serial clinical, radiologic (CT imaging), and functional features (level-of-care, oxygen requirement) were collected preadditional and postadditional immunosuppression.ResultsOf 65 patients with ICI-pneumonitis, 18.5% (12/65) had steroid-refractory ICI-pneumonitis. Mean age at diagnosis of ICI-pneumonitis was 66.8 years (range: 35–85), 50% patients were male, and the majority had lung carcinoma (75%). Steroid-refractory ICI-pneumonitis occurred after a mean of 5 ICI doses from PD-(L)1 start (range: 3–12 doses). The most common radiologic pattern was diffuse alveolar damage (DAD: 50%, 6/12). After corticosteroid failure, patients were treated with: IVIG (n=7), infliximab (n=2), or combination IVIG and infliximab (n=3); 11/12 (91.7%) required ICU-level care and 8/12 (75%) died of steroid-refractory ICI-pneumonitis or infectious complications (IVIG alone=3/7, 42.9%; infliximab alone=2/2, 100%; IVIG + infliximab=3/3, 100%). All five patients treated with infliximab (5/5; 100%) died from steroid-refractory ICI-pneumonitis or infectious complications. Mechanical ventilation was required in 53% of patients treated with infliximab alone, 80% of those treated with IVIG + infliximab, and 25.5% of those treated with IVIG alone.ConclusionsSteroid-refractory ICI-pneumonitis constituted 18.5% of referrals for multidisciplinary irAE care. Steroid-refractory ICI-pnuemonitis occurred early in patients’ treatment courses, and most commonly exhibited a DAD radiographic pattern. Patients treated with IVIG alone demonstrated an improvement in both level-of-care and oxygenation requirements and had fewer fatalities (43%) from steroid-refractory ICI-pneumonitis when compared to treatment with infliximab (100% mortality).