Infliximab - A Saviour in Severe Early Onset Durvalumab-Induced Pneumonitis?

Document Type

Conference Proceeding

Publication Date

10-2024

Publication Title

Chest

Abstract

INTRODUCTION: Checkpoint inhibitor Pneumonitis (CIP) is rare but potentially fatal toxicity of PD1/PDL1 immunotherapy, defined as the occurrence of respiratory symptoms/signs with new infiltrates on imaging and exclusion of new infections on sputum and/or bronchoalveolar lavage (BAL) testing. It is stratified into 5 grades based on severity. We present a case of grade 4 Durvalumab-induced pneumonitis. CASE PRESENTATION: A 76-year-old woman presented to our emergency department with worsening Shortness of breath and exertional intolerance. Her past medical history is significant for recently diagnosed RLL Stage IIB (cT2aN1M0) non-small cell lung cancer (NSCLC), severe emphysema, tobacco abuse, and colon adenocarcinoma post hemicolectomy. Her NSCLC was biopsy proven to be sarcomatoid Carcinoma. She was treated with concurrent chemoradiation for 5 weeks and started consolidation immunotherapy with Durvalumab, and presented 2 weeks later with the above symptoms. Initial workup revealed hypoxia at 82% with new patchy bilateral consolidative and ground glass opacities on CTA-PE, due to concern for Pneumonia and/or immunotherapy Pneumonitis, she was started on broad spectrum antimicrobials- cefepime and vancomycin; and steroids at a dose of 2mg/kg. Given the inability to wean her oxygen and no improvement in interval imaging, she underwent bronchoscopy with BAL, and her antibiotic coverage was broadened to include meropenem, micafungin, and prophylactic bactrim for PJP prophylaxis. However, infectious workup on BAL, including fungal, AFB, and Pneumocystis, was negative and empiric antibiotics were discontinued. Additional workup for acute respiratory failure, including echocardiogram with bubble study, was negative for PFO, and heart function was normal. Her oxygen requirements kept on increasing post-BAL, and she was requiring 100% Fio2 by high flow nasal cannula with intermittent desaturations in the 80s. After discussion with Oncology, she was treated with one dose of infliximab; however, her medical condition was refractory to the above treatment, and we decided to start her on pulse dose steroids and, 2 days following that, repeated infliximab. Despite extensive workup and treatment, patient continued to decline. Due to her poor prognosis and minimal chance of recovery patient opted to pursue comfort measures initially however as her oxygen requirement and clinical status improved within hospice ,patient enrolled out and was able to be discharged to SAR with pulmonary rehab and a prolonged steroid taper course. She was followed up in clinic and has been stable on 3-4L of Oxygen for almost a year. DISCUSSION: Immunotherapy has revolutionized the treatment of advanced NSCLC; however, significant toxicities have been reported, with CIP being particularly worrisome and potentially lethal. Diagnosis can be challenging on account of coexisting primary malignancy and often pneumonia. We report a case of severe, treatment-refractory Durvalumab-induced pneumonitis with unusually fast onset. Median onset time is usually 2.8 months with a wide range of 9 days to 19 months. However, most cases reported in the < 30-day range are grade 1-2 with excellent response to steroids. Infliximab has been used in some cases of CIP and could be a significant factor in improvement of outcomes. CONCLUSIONS: Further research is warranted to understand the pathophysiology, risk factors, and biomarkers of CIP and optimize diagnosis and management.

Volume

166

Issue

4 Suppl

First Page

A346

Comments

Chest 2024 Annual Meeting, October 6-9, 2024, Boston, MA

Last Page

A347

DOI

10.1016/j.chest.2024.06.2637

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