内容紹介
Management of Toxicities of Immune Checkpoint Inhibitors
Summary
Immune checkpoint inhibitors, including the anti-CTLA-4 antibody ipilimumab, the anti-PD-1 antibodies nivolumab and pembrolizumab, and the anti-PD-L1 antibody atezolizumab had produced long-lasting tumor responses in several malignancies. Immune-related Adverse Events(irAEs)which are different from adverse events of conventional chemotherapy and molecular targeted therapy, occur as a consequence of impaired self-tolerance from loss of T-cell inhibition. The main irAEs of immune checkpoint inhibitors include dermatological, gastrointestinal, pulmonary, hepatic, endocrine, renal toxicities. Every organ system can be potentially involved, but nivolumab, pembrolizumab and atezolizumab have a different toxicity profile with fewer high grade events compared with ipilimumab. In this article, we provide an approach to appropriate management for each class of irAEs.
要旨
抗CTLA-4抗体のイピリムマブ(ヤーボイ®),抗PD-1抗体のニボルマブ(オプジーボ®)とペンブロリズマブ(キイトルーダ®),抗PD-L1抗体のアテゾリズマブ(テセントリック®)などの免疫チェックポイント阻害剤は,いくつかの悪性腫瘍で長期に持続する奏効を示す。自己(免疫)寛容の障害の結果として,既存の化学療法や分子標的治療と比較して様式の異なる有害事象が生じ,免疫関連有害事象(immune-related Adverse Event: irAE)として評価されている。全身のすべての臓器でirAEが発生する可能性があるが,ニボルマブとペンブロリズマブとアテゾリズマブはイピリムマブよりもグレード3/4の有害事象の頻度は低い。本稿ではirAEの適切な管理について述べる。
目次
Summary
Immune checkpoint inhibitors, including the anti-CTLA-4 antibody ipilimumab, the anti-PD-1 antibodies nivolumab and pembrolizumab, and the anti-PD-L1 antibody atezolizumab had produced long-lasting tumor responses in several malignancies. Immune-related Adverse Events(irAEs)which are different from adverse events of conventional chemotherapy and molecular targeted therapy, occur as a consequence of impaired self-tolerance from loss of T-cell inhibition. The main irAEs of immune checkpoint inhibitors include dermatological, gastrointestinal, pulmonary, hepatic, endocrine, renal toxicities. Every organ system can be potentially involved, but nivolumab, pembrolizumab and atezolizumab have a different toxicity profile with fewer high grade events compared with ipilimumab. In this article, we provide an approach to appropriate management for each class of irAEs.
要旨
抗CTLA-4抗体のイピリムマブ(ヤーボイ®),抗PD-1抗体のニボルマブ(オプジーボ®)とペンブロリズマブ(キイトルーダ®),抗PD-L1抗体のアテゾリズマブ(テセントリック®)などの免疫チェックポイント阻害剤は,いくつかの悪性腫瘍で長期に持続する奏効を示す。自己(免疫)寛容の障害の結果として,既存の化学療法や分子標的治療と比較して様式の異なる有害事象が生じ,免疫関連有害事象(immune-related Adverse Event: irAE)として評価されている。全身のすべての臓器でirAEが発生する可能性があるが,ニボルマブとペンブロリズマブとアテゾリズマブはイピリムマブよりもグレード3/4の有害事象の頻度は低い。本稿ではirAEの適切な管理について述べる。