Pembrolizumab Therapy Triggering an Exacerbation of Preexisting Autoimmune Disease: A Report of 2 Patient Cases.

Sneha D Phadke,Brian L Swick,Mohammed Milhem,Ramez Ghabour,Andrea Swenson,Yousef Zakharia

doi:10.1177/2324709616674316

Abstract

Historically, metastatic melanoma was uniformly and rapidly lethal, and treatment options were limited. In recent years, however, checkpoint inhibitors have emerged as an accepted standard treatment for patients with advanced melanoma. In clinical trials, these agents have been largely well tolerated and have the potential to result in durable responses. Importantly though, one must recognize the unique side effect profile of these therapies, which can trigger or exacerbate underlying autoimmune disease. Whether this autoimmune activation is associated with a clinical response to therapy has been debated, and while not definitive, there is evidence in the literature of a possible association. The 2 cases presented describe this autoimmune phenomenon, along with a review of the existing literature on the relationship between response to immunotherapy and autoimmune side effects.

Highlights

Immunotherapy using interleukin-2 (IL-2) has long been a part of our historically small armamentarium against advanced melanoma
We present 2 patients with metastatic melanoma treated with the PD-1 checkpoint inhibitor pembrolizumab who developed exacerbations of preexisting autoimmune disease
After careful discussion with the patient about the potential side effects of treatment including worsening of psoriasis, methotrexate was discontinued and pembrolizumab was initiated at 2 mg/kg every 3 weeks

Summary

Introduction

Immunotherapy using interleukin-2 (IL-2) has long been a part of our historically small armamentarium against advanced melanoma. After careful discussion with the patient about the potential side effects of treatment including worsening of psoriasis, methotrexate was discontinued and pembrolizumab was initiated at 2 mg/kg every 3 weeks. Three doses into his treatment, the patient presented with bilateral lower extremity weakness. Punch biopsy of a lesion on the right leg demonstrated psoriasiform epidermal hyperplasia with parakeratosis and intraepidermal pustules confirming the diagnosis of psoriasis (Figure 2) He had no signs or symptoms of worsening psoriatic arthritis. Pertinent medical history included acetylcholine receptor (AChR) autoantibody positive myasthenia gravis (MG) diagnosed at age 64 At that time, he had primarily ocular symptoms and AChR binding antibodies were positive at a titer of 2.1 nmol/L (normal range = 0.0-0.4 nmol/L).

Discussion

Findings

Conclusion