Deceptive Lungs: Is it Brentuximab Induced Pneumonitis or Pneumonia

Introduction: Pulmonary toxicity can be a lethal side effect associated with many newer anti-cancer agents especially immune checkpoint inhibitors. In the times of ever-growing patient population on precision oncology therapies, timely identification of drug induced lung injury can be challenging. Here we highlight pulmonary toxicity as an adverse effect of brentuximab vedotin (BV). Case Report: A 70-year-old male, former smoker with a recent diagnosis of advanced stage classic Hodgkin's lymphoma recently started on BV, presented with two days of progressive dyspnea, fever and productive cough. He denied exposure to sick contacts and recent travel. Of note, he was hospitalized ten days earlier for suspected pneumonia and had completed a course of antibiotics. Vital signs were notable for temperature 101.7°F, heart rate 110 beats/minute, respiratory rate 30 breaths/minute and oxygen saturation of 90% on 6L of oxygen. Physical examination was noteworthy for bibasilar rhonchi. Lab workup was unremarkable and COVID-19 test was negative. Imaging studies displayed new bilateral basal infiltrates on CXR and CT scan of the chest demonstrated new alveolar opacities involving the lower lobes, and interval improvement was noted in the upper lobe opacities. He was treated for presumed pneumonia with broad spectrum antibiotics. However, his oxygen requirements continued to increase, necessitating a further infectious and rheumatologic workup which was negative. After thorough diagnostic evaluation, in the absence of other plausible etiology, the patient's symptoms were attributed to pneumonitis secondary to the chemotherapeutic agent BV. Henceforth, intravenous steroids were initiated which resulted in clinical improvement. Further treatment with BV was withheld and he was discharged on a steroid taper. One month later, a subsequent CT scan of the chest demonstrated complete resolution of bilateral alveolar opacities. Discussion: BV is a CD30 directed antibody-drug conjugate used in advanced or refractory classic Hodgkin's lymphoma. It is known to cause a higher rate of pulmonary toxicity when combined with bleomycin containing regimens with a reported incidence of 40%, hence this combination is contraindicated. However, the incidence of pneumonitis is noted to be only 5% in patients receiving BV in combination with non-bleomycin regimens, which was the case in our patient in lieu of his two back-to-back hospitalizations after receiving two cycles of BV. The exact mechanism of action is unclear but is probably due to hypersensitivity pneumonitis. Although it is a diagnosis of exclusion, a high degree of suspicion is crucial for prompt cessation of the drug in order to prevent adverse outcomes.