SINGLE-DOSE DURVALUMAB INDUCED SARCOIDOSIS-LIKE REACTION WITH GRANULOMA IN NON-SMALL CELL LUNG CANCER

Abstract

SESSION TITLE: Medical Student/Resident Lung Cancer Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: PD-1 inhibitors are revolutionizing the way oncology is practiced in a variety of cancer types. While there are fewer, side effects than chemotherapy, they are not without immune-related adverse events (irAE). These adverse events can affect organ systems such as the GI tract, liver, nervous system and lungs. Pneumonitis is an uncommon iRAE, with about a 3.6% incidence. The differential for pneumonitis includes organizing pneumonia, mycoplasma, radiation therapy, and ICI use. Multiple etiologies can produce clinical and radiological similarities with features similar to pneumonitis such as organizing pneumonia, radiation, and sarcoid-like reaction (SLR). SLR, like pneumonitis, is treated with steroids. In most cases symptoms resolve and ICI use can resume. Biopsy and bronchoscopy are not indicated unless the underlying cause cannot be identified. As evidenced in our case, changes on imaging in patients with ICI's need to be monitored and treated appropriately. CASE PRESENTATION: We present the case of a 60-year-old female with stage IIIb T3N2M0, histologic grade 3, EGFR and ALK/ROS negative NSCLC that received one dose of Durvalumab and developed pneumonitis with underlying SLR 15 days after initiation. She received 4 cycles of Carboplatin/Pemetrexed with concurrent radiation followed by Durvalumab. There was a significant reduction in tumor size from her initial PET/CT scan in terms of her cancer. Epithelioid granulomas were found on biopsy 15 days after Durvalumab initiation. She then developed respiratory failure with subsequent expiration. DISCUSSION: To our knowledge, this is the first reported case of Durvalumab induced SLR after one cycle. In a majority of similar cases, patients' status did not deteriorate as rapidly and dramatically. Image changes with ICI’s raise suspicion for pneumonitis. The effects of prior radiation leading to SLR warrant investigation, and may have contributed. Diagnosis was complicated by bilateral ground glass appearance seen with pneumonitis, contrasted with SLR typically manifesting with focal consolidations. Etiologies such infection, underlying ILD and malignancy should be ruled out. Non-caseating granulomas are a hallmark of sarcoidosis. TH17 cells have been implicated in promotion of cellular recruitment and sustained inflammation in granulomas, whereas Tregs have anti-inflammatory properties. ICI’s promote increased Treg attenuation to allow the host immune system to recognize malignant cells. This in turn relegates Th17 cells to induce pro inflammatory states seen in granuloma formation. We surmise ICI use creates a microenvironment conducive to granuloma formation by disrupting this Th17 vs Treg equilibrium. CONCLUSIONS: High suspicion needs to be taken when patients on ICI’s when there are changes on imaging. Although bronchoscopy and biopsy are not indicated, clinical judgment needs to be exercised to determine possible underlying etiologies. Reference #1: Anderson R, Theron AJ, Rapoport BL. Immunopathogenesis of Immune Checkpoint Inhibitor-Related Adverse Events: Roles of the Intestinal Microbiome and Th17 Cells. Frontiers in Immunology. 2019;10. doi:10.3389/fimmu.2019.02254 Reference #2: Cho JY, Kim J, Lee JS, et al. Characteristics, incidence, and risk factors of immune checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer. Lung Cancer. 2018;125:150-156. doi:10.1016/j.lungcan.2018.09.015 Reference #3: Khunger, M., Rakshit, S., Pasupuleti, V., Hernandez, A. V., Mazzone, P., Stevenson, J., … Velcheti, V. (2017). Incidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer. Chest, 152(2), 271–281. doi: 10.1016/j.chest.2017.04.177 DISCLOSURES: No relevant relationships by raman desikan, source=Web Response no disclosure on file for Krishna Kakkera; No relevant relationships by Philip Sobash, source=Web Response