Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy

Zimmer L., Goldinger S., Hofmann L., Loquai C., Ugurel S., Thomas I., Schmidgen M., Gutzmer R., Utikal J., Göppner D., Hassel J., Meier F., Tietze J., Forschner A., Weishaupt C., Leverkus M., Wahl R., Dietrich U., Garbe C., Kirchberger M., Eigentler T., Berking C., Gesierich A., Krackhardt A., Schadendorf D., Schuler G., Dummer R., Heinzerling L.

Abstract

Background Anti-programmed cell death 1 (PD-1) antibodies represent an effective treatment option for metastatic melanoma and other cancer entities. They act via blockade of the PD-1 receptor, an inhibitor of the T-cell effector mechanisms that limit immune responses against tumours. As reported for ipilimumab, the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects can involve skin, gastrointestinal tract, liver, the endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential. Methods and findings In total, 496 patients with metastatic melanoma from 15 skin cancer centres were treated with pembrolizumab or nivolumab. Two hundred forty two side-effects in 138 patients have been analysed. In 77 of the 138 patients side-effects affected the nervous system, respiratory tract, musculoskeletal system, heart, blood and eyes. Not yet reported side-effects such as meningo-(radiculitis), polyradiculitis, cardiac arrhythmia, asystolia, and paresis have been observed. Rare and difficult to manage side-effects such as myasthenia gravis are described in detail. Conclusion Anti-PD-1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity.