Novel Melanoma Therapies and Their Side Effects
In the last few years, melanoma treatment has been revolutionized by the development of immune checkpoint–blocking antibodies or immune checkpoint inhibitors including ipilimumab, vemurafenib, dabrafenib, trametinib, nivolumab, and pembrolizumab. Although they have shown promising results, they also have caused multiple adverse events (AEs), particularly immune-related AEs (irAEs). Specialists should be familiar with these AEs.
Practice Points
- Immune checkpoint inhibitors can cause immune-related adverse events (irAEs), which most commonly involve the skin but also involve the gastrointestinal, hepatic, endocrine, and neurologic systems.
- These irAEs can be treated with corticosteroids, tumor necrosis factor α antagonists, and mycopheno-late mofetil.
It is unclear whether immunomodulating agents exacerbate autoimmune diseases. Patients with autoimmune diseases were not included in the clinical trials but reportedly have been treated with ipilimumab without exacerbations. Nevertheless, there has been a report of worsening multiple sclerosis in a melanoma patient treated with ipilimumab.39
Conclusion
Immunomodulators have dramatically improved the survival and care of patients with unresectable melanomas. Because of their mechanism of action, they have the capability to produce substantial toxicity. Although most AEs are mild, lethal side effects can ensue. Therefore, all specialists treating patients with melanoma should be familiar with these side effects and their treatment options, as survival rates and survival times will be increasing over the next few years. Rapid AE identification and treatment can improve patient outcomes and optimize the therapeutic potential of these medications. Because immune checkpoint inhibitors are fairly new, further studies are needed to assess irAEs and the long-term impact in patients treated with immunomodulators.
