View Abstract

A6612 - Nivolumab Induced Granulomatous Reaction
Author Block: K. Pal1, H. C. Malpass1, M. Hanley2, W. W. Grosh3; 1Pulmonary and Critical care, University of Virginia, Charlottesville, VA, United States, 2Radiology, University of Virginia, Charlottesville, VA, United States, 3Hematology and Oncology, University of Virginia, Charlottesville, VA, United States.
Introduction
Check point inhibitors (CI) are now commonly and successfully used as targeted immunotherapy for many malignancies. Nivolumab (N) is a human IgG4 Programmed cell death-1 (PD-1) monoclonal antibody inhibitor (Mab) that is used for the treatment of numerous malignancies including malignant melanoma, non-small cell lung cancer, renal cell carcinoma, Hodgkin’s disease and mismatch repair deficient malignancies. The most commonly described side effects of N are rash, fatigue, diarrhea, arthralgia and nausea.
Case
We report a case of a 53 year old woman with a complicated oncological history who presented with an undifferentiated malignancy first classified as a sarcoma but later reclassified as a metastatic non-small cell lung cancer. She had progressive disease after first line chemotherapy and radiation and eventually received N therapy 240mg IV every 2 weeks for 10 cycles. She had widely metastatic disease with multiple pulmonary nodules on computed tomography (CT) scan of her chest prior to treatment. After her 10th cycle there was almost complete resolution of her pulmonary nodules on CT, however, she developed new bilateral hilar lymphadenopathy with increased FDG activity on positron emission tomography (PET) scan. The patient had symptomatically improved from therapy with no new recent illnesses or respiratory infections. She underwent a bronchoscopy with Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA), cultures were negative for bacteria and fungi but cytopathology demonstrated sarcoid-like granulomatous inflammation. Her therapy is currently on hold due to autoimmune diarrhea undergoing therapy with steroids.
Discussion
Immune related adverse events such as sarcoid like granulomatous reactions have been described with other CI such as the anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) Mab and anti-PD1 Mab. A pulmonary sarcoid-like reaction from N monotherapy has only been previously described in one other case report. N selectively inhibits PD-1 activity by binding to the PD-1 receptor and blocks the ligands (PD-L1 and PD-L2) from binding to their receptor. This disrupts the suppressive signaling and restores antitumor immunity. Sarcoid reactions have been described in combination therapies with anti-CTLA4 and anti-PD-1 Mab but our case demonstrates that these granulomatous reactions can occur independently of the CTLA-4 pathway.
Conclusion
Sarcoid-like granulomatous reactions may be mistakenly interpreted as disease progression or new malignancy in patients on therapy. CI have revolutionized anti-neoplastic therapy due to their mechanism of action. It is critical for pulmonologists and oncologists to recognize the potential side effects of CI such as described in our case to accurately interpret outcomes.