Zusammenfassung
Das Spektrum der Tumoren, bei denen eine Checkpointinhibitor(CI)-Therapie eingesetzt wird, erweitert sich stetig. Die Europäische Arzneimittelagentur hat derzeit 9 CIs zugelassen: 1 Anti-CTLA-4(„anti-cytotoxic T lymphocyte-associated antigen 4“)-CI, 1 Anti-LAG-3(„anti-lymphocyte activation gene 3“)-CI, 4 Anti-PD-1(„anti-programmed cell death protein 1“)-CIs und 3 Anti-PD-L1(„anti-programmed death ligand 1“)-CIs. Durch die Blockade von Immuncheckpoints wird die physiologische Herabregulierung einer T‑Zell-Aktivität gegen körpereigene Strukturen verhindert. Es resultiert eine immunologisch unregulierte Aktivierung von T‑Zellen, die sich gegen bösartig entartete Zellen richten soll. Auch gesundes Gewebe exprimiert Antigene und aktiviert dadurch ständig körpereigene T‑Zellen. So kann die Blockade von Immuncheckpoints zu einer T‑Zell-Aktivität gegen gesundes Gewebe („immunbedingte unerwünschte Ereignisse“ [irAEs]) führen. Die irAEs können in jedem Organsystem auftreten, und etwa 10 % aller Patient:innen unter CI-Therapie entwickeln rheumatologische irAEs, meist Arthralgien und Myalgien. Die Klassifikationskriterien rheumatologischer Erkrankungen müssen nicht erfüllt werden, um eine Therapie einzuleiten, und das oberste Ziel der Therapie von irAEs ist die Möglichkeit, die CI-Therapie fortzusetzen. Rheumatologische irAEs sollten schnell erkannt und behandelt werden. In der Therapie der muskuloskeletalen irAEs können 3 Stufen festgelegt werden. In der ersten Stufe werden nichtsteroidale entzündungshemmende Medikamente oder intraartikuläre sowie systemische Glukokortikoide angewendet. In der zweiten Stufe kommen konventionelle synthetische und in der dritten Stufe biologische krankheitsmodifizierende Antirheumatika zum Einsatz. Die gravierendste muskuloskeletale irAE ist die Myositis mit einer kardialen und/oder respiratorischen Beteiligung und/oder einer Myasthenia gravis. In der Therapie werden neben Hochdosisglukokortikoiden auch intravenöse Immunglobuline oder ein Plasmaaustausch eingesetzt.
Abstract
The spectrum of tumors for which checkpoint inhibitor (CI) treatment is used is constantly expanding. The European Medicines Agency has currently approved nine CIs: one anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) CI, one anti-lymphocyte activation gene 3 (LAG-3) CI, four anti-programmed cell death protein 1 (PD-1) CIs and three anti-programmed death ligand 1 (PD-L1) CIs. By blocking immune checkpoints the physiological downregulation of T cell activity against autologous tissue is prevented. This results in an immunologically unregulated activation of T cells directed against malignant cells. Healthy tissue also expresses antigens and thereby continuously activates autologous T cells. Thus, the blockade of immune checkpoints can lead to T cell activity against healthy tissue (immune-related adverse events, irAE). The irAEs can occur in any organ system and approximately 10% of all patients under CI treatment develop rheumatological irAEs, mostly arthralgia and myalgia. The classification criteria of rheumatological diseases do not need to be met to initiate treatment and the primary goal of treatment of irAEs is to enable continuation of CI treatment. Rheumatological irAEs should be recognized and treated quickly. In the treatment of musculoskeletal irAEs, three stages can be defined. In the first stage, nonsteroidal anti-inflammatory drugs or intra-articular as well as systemic glucocorticoids are used. In the second stage, conventional synthetic and in the third stage, biologic disease-modifying antirheumatic drugs are used. The most severe musculoskeletal irAE is myositis with cardiac and/or respiratory involvement and/or myasthenia gravis. In addition to high-dose glucocorticoids, intravenous immunoglobulins or plasma exchange are used in treatment.
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Grümme, L., Schulze-Koops, H. Rheumatologische Nebenwirkungen von Checkpointinhibitoren und deren Behandlung. Z Rheumatol 82, 187–194 (2023). https://doi.org/10.1007/s00393-022-01311-4
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DOI: https://doi.org/10.1007/s00393-022-01311-4