Immunotherapy Induced Pneumonitis

Abstract

INTRODUCTION: Pneumonitis is focal or diffuse inflammation of lung parenchyma. With recent advancements in oncology, immunotherapy is an emerging cause of pneumonitis. Atezolizumab is an immune checkpoint inhibitor (ICI) that targets PD-L1 to prevent the interaction with receptors PD-1 and B7-1, thus reversing T-cell suppression and can cause pneumonitis due to the inflammatory response. It has an incidence of up to 10%. Symptoms can include dyspnea (53%), cough (35%), fever (12%), and chest pain (7%). CASE: An 81-year-old male with unresectable hepatocellular carcinoma (HCC) on Atezolizumab-Bevacizumab, intra-lesional hematoma, and portal vein thrombosis presented with one day of dyspnea. In the ED, he was found to be hypoxic to 80% on room air. The examination was unremarkable except for bilateral crackles on auscultation. Laboratory tests including complete blood count, electrolytes, liver function tests, kidney function tests, and arterial blood gas were within normal limits. CT chest revealed bilateral multifocal airspace opacities. Due to the acute hypoxemic respiratory failure, he was transferred to the ICU for care. Blood cultures were sent. Antibiotic therapy with vancomycin, cefepime, and azithromycin was initiated for presumed community-acquired pneumonia. The patient continued to worsen clinically. All initial infectious workup was negative including blood cultures, tuberculosis and fungal workup, and respiratory viral pathogen PCR. COVID-19 and influenza PCR was negative thrice. Of note, the patient completed his second cycle of immunotherapy with Atezolizumab-Bevacizumab, four days prior to admission. He was started on methylprednisolone 2mg/kg/d on hospital day (HD) 5 for likely ICI-induced pneumonitis. Despite steroid therapy, no clinical improvement was noted. He was additionally given a single dose of infliximab 5mg/kg to which he improved clinically initially. However, he later grew Aspergillus in his bronchoalveolar lavage and passed away from multi-organ failure on HD 22. DISCUSSION: We describe a case of HCC with hematoma. Given the risk of bleeding with first-line therapy (Sorafenib), a combination of Atezolizumab-Bevacizumab was used instead. ICI-induced pneumonitis is a diagnosis of exclusion with no specific clinical picture or radiologic findings. Anti-VEGF antibodies like Bevacizumab are more likely to cause pulmonary hemorrhage than pneumonitis. ICI-induced pneumonitis is divided into 4 grades. This patient was categorized as Grade 3. The patient received infliximab as he did not respond to initial therapy consisting of empirical antibiotics and IV methylprednisolone. In patients on ICI, who present with respiratory symptoms, clinicians should have a high degree of suspicion for pneumonitis. Early diagnosis and treatment could potentially reduce mortality.