NIVOLUMAB-INDUCED PNEUMONITIS WITHIN 4 DAYS OF INITIATION OF THERAPY

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Nivolumab is an FDA approved drug for use in metastatic NSCLC that has progressed despite platinum-based chemotherapy. Our patient had an episode of Nivolumab induced pneumonitis within 4 days of therapy making it complicated to distinguish it from an infectious process. CASE PRESENTATION: A 77-year-old man with the past medical history of a pulmonary embolism on apixaban at home and metastatic non-small cell lung carcinoma (NSCLC) presented to the hospital with the chief complaint of shortness of breath. The patient was on immunotherapy with Nivolumab and had received 8 cycles of immunotherapy. The last session of immunotherapy was 4 days prior to presentation. On presentation, he was tachypneic at 26 breaths per minute and was placed on 6 liters of oxygen by nasal cannula to maintain spO2 >92 %. Examination showed decreased breath sounds bilaterally in the bases as well as crackles throughout the lung fields. ABG showed hypoxemia with respiratory alkalosis with a PH of 7.51, PaO2 50, PaCO2 of 30, HCO3 22.1. CT angiogram of the chest showed right lower lobe lung mass, obstruction of the right lower lobe branch vessel which appeared old and bilateral diffuse interstitial lung disease with ground-glass appearance. However, no new pulmonary embolism was observed. The patient was started empirically on ceftriaxone and azithromycin to cover for community-acquired pneumonia. Patient had an extensive infectious workup including viral, bacterial, fungal, mycobacterial as well as autoimmune workup which was negative. In the light of negative infectious workup and procalcitonin<0.05, Antibiotics were stopped, and the patient was started on high-dose Intravenous hydrocortisone and managed symptomatically. He was slowly weaned off the oxygen and discharged home with an oral steroid taper. In light of the temporal correlation of interstitial lung disease with nivolumab administration, no evidence of any other pathology infectious/noninfectious and resolution of the disease with drug abstinence, the patient was diagnosed with Nivolumab induced interstitial Pneumonitis. The Naranjo score was calculated to be 9 indicating a definite adverse drug reaction. DISCUSSION: Nivolumab induced pneumonitis has a reported incidence of 2.9% if used alone and 11.8% if used in combination. The median time of incidence reported is between 9 days to 19 months. Our patient had pneumonitis within 4 days of nivolumab therapy making it difficult to differentiate from an infectious process. The reason for early presentation in our patient remains unknown. Currently, there are no guidelines for the treatment of Nivolumab induced pneumonitis. Steroids and abstinence from nivolumab are the mainstays of therapy. CONCLUSIONS: Clinicians should be mindful that Nivolumab induced pneumonitis can present as early as 4 days after initiation of therapy. However, other causes of dyspnea should be ruled out before diagnosing it. Reference #1: Michot J. M., Bigenwald C., Champiat S., et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. European Journal of Cancer. 2016;54:139–148. doi: 10.1016/j.ejca.2015.11.016. Reference #2: Nishino M, Ramaiya NH, Awad MM, Sholl LM, Maattala JA, Taibi M, Hatabu H, Ott PA, Armand P, Hodi FS. PD-1 inhibitor-related pneumonitis in advanced cancer patients: radiographic patterns and clinical course. Clin Cancer Res. 2016;22(24):6051-60. Reference #3: Kato T, Masuda N, Nakanishi Y, Takahashi M, Hida T, Sakai H, Atagi S, Fujita S, Tanaka H, Takeda K, et al. Nivolumab-induced interstitial lung disease analysis of two phase II studies patients with recurrent or advanced non-small-cell lung cancer. Lung Cancer. 2017;104:111–8. DISCLOSURES: No relevant relationships by Fazal Raziq, source=Web Response