Autoimmune Myasthenia, Primary Adrenal Insufficiency, and Progressive Hypothyroidism Due to Pembrolizumab and Axitinib Combination Regimen

Nikole Figueroa-Perez,Vishwanath Pattan,Deepinder Bal,Syed Anjum Khan,Rahul Kashyap

doi:10.7759/cureus.16933

Abstract

Immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) have been among the increasingly used antineoplastic agents for advanced cancers including renal cell carcinoma (RCC). Although these antineoplastic agents have broad range of efficacy, rare adverse events - mild and fatal, acute and chronic, immune and non-immune mediated - have been reported. We report a case of a 73-year-old Caucasian male patient with stage IV right-sided clear cell RCC who was treated with a pembrolizumab-axitinib combination regimen and suffered life-threatening, acute onset immune-related myasthenia gravis (MG), subsequently progressive hypothyroidism, and primary adrenal insufficiency.

Highlights

Pembrolizumab is a humanized IgG4 kappa monoclonal antibody that inhibits programmed cell death 1 receptor which has efficacy in numerous malignancies including renal cell carcinoma (RCC) [1]
Combining anti-PD1 immune checkpoint inhibitor (ICI) with tyrosine kinase inhibitor (TKI) of the vascular endothelial growth factor (VEGF) pathway has been characterized by excess toxicity, the combination of axitinib plus pembrolizumab was reported to be tolerable [3]
We report myasthenia gravis, thyrotoxicosis from transient thyroiditis followed by hypothyroidism, and primary adrenal insufficiency as adverse effects from using this combination to treat a patient with clear cell carcinoma

Summary

Introduction

Pembrolizumab is a humanized IgG4 kappa monoclonal antibody that inhibits programmed cell death 1 receptor (anti-PD1 antibody) which has efficacy in numerous malignancies including renal cell carcinoma (RCC) [1]. Eighteen days after starting pembrolizumab (one dose) and 13 days after starting axitinib, the patient presented to the emergency department due to one-week history of progressive fatigue and shortness of breath He complained of a level of fatigue he had never experienced before and even had difficulty holding his head up. The patient had a history of hypothyroidism diagnosed in 2013, with an elevated TSH of 9.25 He was started on levothyroxine 25μg daily. Pembrolizumab was discontinued after the first dose due to myasthenic crisis, the patient’s axitinib dose was maintained, and he required progressive increases in his levothyroxine dosage over time He was on a tapering dose of prednisone since myasthenia gravis was diagnosed. The patient was placed on a replacement dose of hydrocortisone, 15mg in the morning and 10mg in the afternoon, and fludrocortisone 0.1mg daily

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Disclosures