Pneumonitis in Patients Treated With Anti–Programmed Death-1/Programmed Death Ligand 1 Therapy

Abstract

Pneumonitis is an uncommon but potentially fatal toxicity of anti-programmed death-1 (PD-1)/ programmed death ligand 1 (PD-L1) monoclonal antibodies (mAbs). Clinical, radiologic, and pathologic features are poorly described. MethodsPatients who received anti-PD-1/PD-L1 monotherapy or in combination with anti-cytotoxic T-cell lymphocyte-4 mAb were identified at two institutions (Memorial Sloan Kettering Seventy-two percent (31 of 43) of cases were grade 1 to 2, and 86% (37 of 43) improved/resolved with drug holding/immunosuppression. Five patients worsened clinically and died during the course of pneumonitis treatment; proximal cause of death was pneumonitis (n = 1), infection related to immunosuppression (n = 3), or progressive cancer (n = 1). Radiologic and pathologic features of pneumonitis were diverse. ConclusionPneumonitis associated with anti-PD-1/PD-L1 mAbs is a toxicity of variable onset and clinical, radiologic, and pathologic appearances. It is more common when anti-PD-1/PD-L1 mAbs are combined with anti-cytotoxic T-cell lymphocyte-4 mAb. Most events are low grade and improve/ resolve with drug holding/immunosuppression. Rarely, pneumonitis worsens despite immunosuppression, and may result in infection and/or death.

Risk factors for pneumonitis in patients treated with anti‐programmed death‐1 therapy: A case‐control study

“…Clinical study variables, such as inclusion or exclusion criteria, dosage, and stage, varied in these randomized trials, potentially limiting an accurate interpretation of the results. In addition, a similar incidence among patients with melanoma or NSCLC for monotherapy or combination therapy was revealed in a previous observational study 16. Consistent with this finding, no significant association between lung cancer and ICB‐related pneumonitis was detected in this study.…”

“…To the best of our knowledge, this is the first case‐control study systematically seeking to identify risk factors for anti‐PD‐1 mAbs‐related pneumonitis development in a Chinese population of multiple types of advanced cancer. This study fills an important gap in the literature and supplements the limited number of published reports on anti‐PD‐1 pneumonitis 5, 16, 17, 18…”

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

“…181 Immune-related AEs, such as pneumonitis, may occur with immune checkpoint inhibitors. 173,178,[182][183][184][185][186][187][188][189] Intravenous high-dose corticosteroids should be administered based on the severity of the reaction for patients with immune-mediated AEs. Immune checkpoint inhibitors should be discontinued for patients with severe or life-threatening pneumonitis and should be withheld or discontinued for other severe or life-threatening immune-mediated AEs when indicated (see prescribing information).…”

Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma

“…In a recent study of 915 patients who received anti-PD-1 antibodies as a monotherapy, pneumonitis developed in 5% of patients, whereas those receiving combination immunotherapy had a 10% incidence of pneumonitis. 32 In our study, only 1 patient had grade 3 pneumonitis. All 6 patients responded to drug interruption alone (n 5 3) or after a short (2 week) course of steroids (n 5 3); 2 patients had recurrent episodes and stopped therapy.…”