Immune Checkpoint Inhibitor Induced Pericarditis and Encephalitis in a Patient Treated With Ipilimumab and Nivolumab for Metastatic Melanoma: A Case Report and Review of the Literature

Jorja Braden,Jenny H Lee

doi:10.3389/fonc.2021.749834

Abstract

Immune checkpoint inhibitors (ICIs) have dramatically improved outcomes in melanoma. Common ICI toxicities have become familiar to clinicians; however, rare delayed toxicities remain challenging given the paucity of data with such presentations. We present the unique case of a 61-year-old with metastatic melanoma with two rare, delayed ICI-induced toxicities. After resection of a large symptomatic parietal metastases, this patient received two doses of combination ipilimumab and nivolumab. Five weeks following his second dose, he developed ICI-induced pericarditis with associated pericardial effusion and early signs of tamponade. Corticosteroids were not administered due to a concurrent cerebral abscess. Administration of colchicine, ibuprofen, judicious monitoring, and cessation of immunotherapy led to the complete resolution of the effusion over several weeks. Seven months following his last dose of immunotherapy, the patient developed ICI-associated grade four autoimmune encephalitis, presenting as status epilepticus. High-dose steroid initiation led to rapid clinical improvement. The patient remains in near-complete response on imaging with no recurrence of pericardial effusion and partial resolution of neurological symptoms. ICI-induced pericardial disease and encephalitis carry substantial mortality rates and prompt diagnosis and management is critical. Clinicians must therefore remain vigilant for these rare toxicities regardless of duration of drug exposure or time since cessation of therapy.

Highlights

The combination of immune checkpoint inhibitors (ICIs) ipilimumab and nivolumab have drastically improved outcomes for advanced melanoma patients with 5-year survival rates of 52% [1]
The combination is associated with higher rates of a broad range of ICI-induced toxicities when compared to Checkpoint Inhibitor Induced Pericarditis and Encephalitis single-agent checkpoint inhibition, contributing to higher morbidity and mortality in these patients [1, 2]
We report the case of a patient with two sequential rare ICI-associated toxicities of grade 3 pericarditis and grade 4 encephalitis presenting 1.5 months and 7.5 months after brief exposure to ipilimumab and nivolumab treatment for metastatic melanoma

Summary

INTRODUCTION

The combination of immune checkpoint inhibitors (ICIs) ipilimumab and nivolumab have drastically improved outcomes for advanced melanoma patients with 5-year survival rates of 52% [1]. We report the case of a patient with two sequential rare ICI-associated toxicities of grade 3 pericarditis and grade 4 encephalitis presenting 1.5 months and 7.5 months after brief exposure to ipilimumab and nivolumab treatment for metastatic melanoma. He proceeded with resection of the right parietal lobe metastases in February followed by ipilimumab (3 mg/kg)/nivolumab (1 mg/kg) commencing in March (Figure 1). Cultures confirmed corynebacterium acnes and he commenced intravenous (IV) Cephalothin for a total of 12 weeks Six weeks following his last dose of immunotherapy and while on IV antibiotics for his cerebral abscess, the patient developed severe peripheral edema, dyspnea, and tachycardia. His pericarditis has not recurred with significant but partial neurological recovery from his grade 4 encephalitis

DISCUSSION

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CONCLUSION

ETHICS STATEMENT