CASE SERIES: SERIOUS PULMONARY TOXICITY SECONDARY TO PEMBROLIZUMAB; AN IMMUNE CHECKPOINT INHIBITOR

Abstract

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Immune checkpoint inhibitors (ICIs) which target the programmed cell death 1 (PD-1) / programmed cell death ligand 1 (PDL-1) pathway [1,2,3] have been effective in cancer treatment. ICIs carry a high risk of lung injury with potential for permanent damage and death [1]. We describe 3 patients with lung injury from use of PD-1 Inhibitor (Pembrolizumab) that outlines the spectrum of injury and outcome. CASE PRESENTATION: Case one:74-year-old male was treated for metastatic urinary bladder carcinoma with pembrolizumab and 2 months later developed nonspecific interstitial pneumonia (NSIP)(Figure 1) leading to hypoxemic respiratory failure requiring ventilator support. This progressed over 1 month to fibrotic NSIP. Course was complicated by Sepsis and multi organ failure and the patient died. Case two:48-year-old male was treated for metastatic renal cell carcinoma with pembrolizumab. Two months later he developed hypoxemic respiratory failure secondary to organizing pneumonia (Figure 2). The drug was discontinued and in spite of treatment with steroids and mycophenolate, he progressed to fibrotic organizing pneumonia and now has poor functional status and is oxygen dependent. Also noted were abnormal liver function, raised troponin and raised lipase suggestive of drug induced toxicity.Case three:74-year-old with metastatic stage IV Non-small cell lung cancer treated with chemotherapy and pembrolizumab. Two months later he developed hypoxemic respiratory failure secondary to organizing pneumonia (Figure 3) but rapidly responded to steroid treatment. DISCUSSION: Patients treated with PD-1 inhibitors such as Pembrolizumab, are high risk for lung injury [1]. Patterns of Injury described include organizing pneumonia, nonspecific interstitial pneumonia (NSIP), Hypersensitivity pneumonitis, acute interstitial pneumonia, radiation recall pneumonitis and bronchiolitis. Median time to occurrence of lung injury is 3 months. More than 50 % of patients also exhibit signs of inflammatory dysfunction in the heart, skin, thyroid or colon. Up to 12% of patients progress to lethal disease despite immunosuppression [2,3]. Two of our patients developed lung injury in the form of organizing pneumonia with one responding to steroids and the other progressing to fibrotic disease and oxygen dependency. The third patient progressed to fibrotic NSIP and died with complications of sepsis and organ failure. CONCLUSIONS: Lung injury secondary to PD-1 inhibitor treatment can lead to severe and lethal outcomes [2,3] and we report our experience to highlight this. Close monitoring is recommended and early discontinuation at first sign of lung injury is essential. Response to immunosuppression is unpredictable and early recognition is the key. Reference #1: 1.Khunger, M. et al. Incidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Trials. Chest 152, 271–281 (2017). Reference #2: 2.Rickard, Frances et al. "Pneumonitis: a serious adverse effect of PD-L1 inhibitors including pembrolizumab.” BMJ case reports vol. 2018 bcr2018224485. 7 May. 2018, https://doi.org/10.1136/bcr-2018-224485 Reference #3: 3.Jun, Jiho et al. "Pneumonitis and concomitant bacterial pneumonia in patients receiving pembrolizumab treatment: Three case reports and literature review.” Medicine vol. 98,25 (2019): e16158. https://doi.org/10.1097/MD.0000000000016158 DISCLOSURES: No relevant relationships by Abdul Basit, source=Web Response No relevant relationships by Aaron Douen, source=Web Response No relevant relationships by Pushpinder Kaur, source=Web Response No relevant relationships by padmanabhan krishnan, source=Web Response No relevant relationships by David Michael, source=Web Response No relevant relationships by Nikolas St.Cyr, source=Web Response