Pembrolizumab-Induced Sarcoid-Like Reaction

Abstract

INTRODUCTION:Pembrolizumab is a humanized monoclonal antibody that targets the programmed cell death-1 receptor in T-cells and is becoming more widely utilized. Immunologic checkpoint inhibitors have revolutionized cancer treatment but can be associated with systemic toxicities, including pyrexia, chills, infusion reactions, and rarely immunologic phenomena such as sarcoid-like reactions [1]. CASE PRESENTATION:We present a case of an 81-year-old female with a history of hypertension, hyperlipidemia, and urothelial carcinoma of the renal pelvis metastatic to the retroperitoneal lymph nodes. She had undergone a right nephrectomy and completed adjuvant chemotherapy with carboplatin plus gemcitabine. Afterward, the oncology team initiated Pembrolizumab IV 200 mg every three weeks for maintenance therapy. Follow-up imaging done four months after starting immunotherapy showed a solid pulmonary nodule in the right lower lobe measuring 3.7 x 2.1 cm. Due to concern for metastasis, she underwent a percutaneous biopsy which revealed non-caseating granulomas. She lacked signs of sarcoidosis such as arthritis, rash, visual change, and mediastinal adenopathy, and a detailed workup for fungal and mycobacterial diseases was negative. Given the recent initiation of pembrolizumab, a medication-induced reaction was considered. DISCUSSION:The differential diagnosis for pulmonary granulomatous disease includes non-infectious etiologies such as sarcoidosis or hypersensitivity pneumonitis, infectious etiologies such as fungal or mycobacterial diseases, and drug-induced reactions. Pembrolizumab is an immune checkpoint inhibitor used in the treatment of malignancy, and it acts by blocking PD-1 located on lymphocytes. Some reports have discussed concerns that pembrolizumab could exacerbate or manifest autoimmune disease [2, ]. Additionally, a few reports have described the development of non-caseating granulomas (referred to as sarcoid-like reaction), 3-6 months after treatment with Pembrolizumab and other checkpoint inhibitors such as ipilimumab and nivolumab [2,3]. The sarcoid-like reaction is primarily T-cell mediated and is a localized process (affecting either the lungs, skin, or kidneys), unlike sarcoidosis, which is more of a systemic disease. However, as it manifests as a new nodule or lymphadenopathy, a biopsy is often required to rule out metastatic disease.CONCLUSIONS: This case highlights the importance of understanding the relationship between immunologic therapies and their range of toxicities. While pembrolizumab is an effective treatment in malignancy, clinicians should be aware of the unexpected immunologic consequences of sarcoid-like reactions or flares of pre-existing autoimmune disease.