Immune Checkpoint Inhibitors in Metastatic Melanoma – Is This too High of a Price?

Liana Chicea^(1,*), Nicoleta Buric⁽²⁾

1)Rheumatology Department, Academic Emergency Hospital Sibiu
2)University Lucian Blaga Sibiu, Romania

Background and aims. Nivolumab is highly effective, as monotherapy or in combinations (with Ipilimumab), for treatment of patients with unresectable or metastatic melanoma and many other cancers. Autoimmune side effects include systemic and organ-specific disease, from mild to life-threatening severity. Their impact on the treatment response may be important.
Methods. We present two advanced melanoma cases, male, 72 and 62 years old. Despite initial tolerability of Nivolumab /Ipilimumab and good response on disease progression, both developed severe autoimmune musculoskeletal side effects.
Case 1. Metastatic melanoma. The tumor size dramatically decreased during nivolumab treatment and over the following 15 weeks. Adverse events were diagnosed by rheumatologists: monoarthritis, severe erythroderma that promptly responded to high-dose glucocorticoids (GC) but rebounded after GC tapering, late onset, non-reversible, rapidly progressive renal failure with haemodialysis and autoimmune progressive pneumonitis with respiratory failure and death.
Case 2. Melanoma stage IV, treated with Nivolumab and Ipilimumab with good response during 6 months, presenting with progressive pain and proximal muscle weakness after discontinuation, had good initial response to GC. Inflammatory immune myopathy, polymyalgia rheumatica and sensitive neuropathy were diagnosed and efficiently controlled with GC treatment and successful oncologic course.
Conclusions. Development of autoimmune disease during checkpoint inhibitor treatment for neoplastic diseases may correlate with efficacy and furthermore impact survival. Rheumatologists may be helpful in checkpoint inhibitors autoimmune side-effects management. Careful and prolonged follow-up, developing protocols and increase patient awareness are essential to improve outcomes. High-dose and long-term GCs may increase mortality.

Keywords: checkpoint inhibitors, autoimmune adverse effects, metastatic melanoma

Corresponding author(s): Liana Chicea, Rheumatology Department, Academic Emergency Hospital Sibiu, Romania; email: liana.chicea@gmail com