DIFFUSE ALVEOLAR HEMORRHAGE FOLLOWING DUAL CHECKPOINT INHIBITOR THERAPY

Abstract

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Immune checkpoint inhibitors (ICIs) have emerged as new therapeutic agents with survival benefit for various cancers, but are associated with various complications (1,2). ICI related pulmonary toxicity usually manifests in the form of pneumonitis, but diffuse alveolar hemorrhage (DAH) caused by ICIs has not been previously described (3). CASE PRESENTATION: A 72-year-old man with history of Diabetes Mellitus, Asthma, Acute Myeloid Leukemia who failed three lines of chemotherapy and bone marrow transplant, was started on ICI therapy with ipilimumab and nivolumab. He was admitted to hospital for worsening night sweats, fatigue and recurrent falls. On day 2, he developed fever, dyspnea, minor hemoptysis (<5mL) and hypoxemia requiring supplemental oxygen (3L via nasal cannula). CT chest revealed bilateral ground-glass infiltrates. He was treated with diuresis and antimicrobials including meropenem and posaconazole. His course was complicated by increasing oxygen requirements (non-invasive ventilation). Extensive infectious workup was negative including blood, urine cultures, respiratory viral panel and fungal serologies. Bronchoalveolar lavage (BAL) performed on day 3 revealed grossly hemorrhagic fluid with no change on 3 sequential lavages. Hemosiderin laden macrophages were reported on the cytologic exam. Of note, he had thrombocytopenia from leukemia, and his platelet count was 13000/cu.mm on the day of bronchoscopy. Following BAL, he was started on IV methylprednisolone 1 mg/kg/day for suspected pneumonitis related to ICI therapy. Within 24 hours, he showed significant improvement in work of breathing and oxygen was weaned to 2L via nasal cannula. BAL culture grew Pseudomonas aeruginosa and vancomycin resistant Enterococcus faecium. He was transitioned to oral steroids was discharged in a stable condition on room air. DISCUSSION: Association of ICIs with pulmonary toxicity in the form of pneumonitis is well recognized. However, DAH has not been described in association with this therapy. We report a case of DAH that appeared after 3 months of ipilimumab and nivolumab treatment. DAH was confirmed through grossly hemorrhagic sequential lavages with the presence of hemosiderin-laden macrophages. Though BAL cultures in this patient showed growth, infection as a cause of DAH is extremely unlikely given progression of disease despite antibiotics and dramatic response to steroids. Further research is needed to elucidate the mechanism and association of DAH in setting of ICI therapy and prognostic and therapeutic implications of such presentation. CONCLUSIONS: Use of immunotherapy for cancer is rapidly expanding, and complications related to such therapy are being increasingly recognized. We describe a case of DAH manifesting with hemoptysis and hypoxic respiratory failure in a patient who was receiving ipilimumab and nivolumab. To our knowledge, this is the first description of such an association. Reference #1: Valadolid J, Amin A. Immune checkpoint inhibitors in clinical practice: update on management of immune-related toxicities. Trans Lung Cancer Res. 2015;4(5):560-75 Reference #2: Suresh, Karthik et al. Pneumonitis in Non–Small Cell Lung Cancer Patients Receiving Immune Checkpoint Immunotherapy: Incidence and Risk Factors Journal of Thoracic Oncology , Volume 13 , Issue 12 , 1930 – 1939 Reference #3: Naidoo J, Wang X, Woo KM, et al. Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2016;35(7):709-717. DISCLOSURES: No relevant relationships by Herbert Berger, source=Web Response No relevant relationships by Vikas Koppurapu, source=Web Response No relevant relationships by Roger Struble, source=Web Response