Immune-checkpoint inhibitors: long-term implications of toxicity

Abstract

The development of immune-checkpoint inhibitors (ICIs) has heralded a new era in cancer treatment, enabling the possibility of long-term survival in patients with metastatic disease, and providing new therapeutic indications in earlier-stage settings. As such, characterizing the long-term implications of receiving ICIs has grown in importance. An abundance of evidence exists describing the acute clinical toxicities of these agents, although chronic effects have not been as well catalogued. Nonetheless, emerging evidence indicates that persistent toxicities might be more common than initially suggested. While generally low-grade, these chronic sequelae can affect the endocrine, rheumatological, pulmonary, neurological and other organ systems. Fatal toxicities also comprise a diverse set of clinical manifestations and can occur in 0.4–1.2% of patients. This risk is a particularly relevant consideration in light of the possibility of long-term survival. Finally, the effects of immune-checkpoint blockade on a diverse range of immune processes, including atherosclerosis, heart failure, neuroinflammation, obesity and hypertension, have not been characterized but remain an important area of research with potential relevance to cancer survivors. In this Review, we describe the current evidence for chronic immune toxicities and the long-term implications of these effects for patients receiving ICIs.

Abstract

Immune-checkpoint inhibitors (ICIs) have dramatically improved the outcomes of patients with advanced-stage solid tumours, including the potential for long-term remission in a subset. However, long-term follow-up data reveal a risk of chronic toxicities from these agents, which can have important quality-of-life implications. In this Review, the authors describe the current level of evidence of chronic toxicities of ICIs and their implications for patients

Key points

• Immune-checkpoint inhibitors (ICIs) produce durable responses in a growing number of patients with metastatic cancer, and are being used increasingly in (neo)adjuvant settings.

• Although acute toxicities are more common, chronic immune-related adverse events (irAEs) are increasingly recognized, and can affect up to 40% of patients.

• Chronic irAEs are mostly classed as endocrine or rheumatological, but can affect a diverse array of organs.

• Other issues with long-term relevance include fatal irAEs (which can occur in 0.4–1.2% of patients), and rechallenge after severe irAEs.

• ICIs could also affect other immune-mediated processes (such as atherosclerosis or neuroinflammation), although more studies are needed.