IMMUNE CHECK POINT INHIBITOR-INDUCED ORGANIZING PNEUMONIA IN A LUNG TRANSPLANT PATIENT

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 check point inhibitors (ICI) are an effective therapy in treatment of multiple malignancies. Ipilimumab, a CTLA-4 antibody was the first ICI to be approved for advanced melanoma, followed by pembrolizumab, a PD1 inhibitor(1)(2). A myriad of immune related adverse effects have been observed with use of checkpoint inhibitors, due to T cell activation. ICI up regulate immune response to cancer but also leads to rejection of transplanted organs. Here we present a case of ICI pneumonitis after treatment with pembrolizumab in a lung transplant patient. CASE PRESENTATION: An 80-year-old Caucasian male received bilateral lung allografts in 2003 for idiopathic pulmonary fibrosis. In 2014, he was diagnosed with malignant melanoma and squamous cell carcinoma of scalp and neck, and underwent wide local excision with radiation therapy. He received two cycles of pembrolizumab for recurrence of melanoma (BRAF wildtype) after which he developed acute hypoxemic respiratory failure requiring mechanical ventilation. The patient received broad spectrum antibiotics and pulse dose methyl prednisolone for suspected transplant rejection. Bronchoalveolar lavage showed bilateral alveolar hemorrhage and trans-bronchial biopsies of the left lower lobe and lingula showed acute organizing pneumonia. With the concern for ICI pneumonitis versus ICI induced rejection of lung allograft the patient was treated with pulse dose steroids and then a prolonged steroid taper. DISCUSSION: Multiple adverse events have been reported with ICI including pulmonary toxicity. In a meta-analysis of 6360 patients, the incidence of pneumonitis from anti-PD-1 immunotherapy was 2.92% (3). Increased T-cell activity, inflammatory cytokines, and enhanced complement-mediated inflammation is suggested as the mechanism. ICI pneumonitis may manifest as cryptogenic organizing pneumonia, interstitial pneumonia, hypersensitivity pneumonitis, or acute respiratory distress syndrome patterns (4). Lung toxicities are graded dependent on severity of symptoms and extent of radiological involvement and American Society of Clinical Oncology provides expert consensus on treatment recommendations. Current guidelines indicated the discontinuation of ICI and initiation of corticosteroids in our patient with grade 3 toxicity. In refractory cases, anti-TNF-a agent infliximab, has been used. Allograft rejection must also be considered in lung transplant patients who undergo ICI therapy. Infectious pneumonia must also be excluded as this can be fatal if left untreated (5). CONCLUSIONS: Our patient presented with ICI related organizing pneumonia in transplanted lungs, which has been reported in few case reports with favorable response to high dose steroids. Awareness of potential complications of ICI especially in transplant population facilitates early recognition and prompt treatment with improved outcomes. Reference #1: 1) Alexander W. The Checkpoint Immunotherapy Revolution: What Started as a Trickle Has Become a Flood, Despite Some Daunting Adverse Effects; New Drugs, Indications, and Combinations Continue to Emerge. P T. 2016;41(3):185–191. Reference #2: 2) Robert, C., Schachter, J., Long, G. V., Arance, A., Grob, J. J., Mortier, L., … Ribas, A. (2015). Pembrolizumab versus Ipilimumab in Advanced Melanoma. New England Journal of Medicine, 372(26), 2521–2532. doi: 10.1056/nejmoa1503093 Reference #3: 3) Nishino M, Giobbie-Hurder A, Hatabu H, Ramaiya NH, Hodi FS. Incidence of Programmed Cell Death 1 Inhibitor–Related Pneumonitis in Patients With Advanced Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2016;2(12):1607–1616. doi:10.1001/jamaoncol.2016.2453 4) Nishino, M., Giobbie-Hurder, A., Hatabu, H., Ramaiya, N. H., & Hodi, F. S. (2016). Incidence of Programmed Cell Death 1 Inhibitor–Related Pneumonitis in Patients With Advanced Cancer. JAMA Oncology, 2(12), 1607. doi: 10.1001/jamaoncol.2016.2453 5) Jun, J., Lee, S. R., Lee, J. Y., Choi, M. J., Noh, J. Y., Cheong, H. J., … Song, J. Y. (2019). Pneumonitis and concomitant bacterial pneumonia in patients receiving pembrolizumab treatment: Three case reports and literature review. Medicine, 98(25), e16158. doi:10.1097/MD.000000000001615 DISCLOSURES: no disclosure on file for Deepa Gotur; No relevant relationships by Uchenne Mbaraonye, source=Web Response no disclosure on file for Cindy Nguyen; no disclosure on file for Lily Romero Karam; Speaker/Speaker's Bureau relationship with Astellas Pharma US, Inc. Please note: $1001 - $5000 Added 03/10/2020 by Simon Yau, source=Web Response, value=Salary