Der Einsatz von Immuncheckpoint-Inhibitoren im onkologischen Alltag

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BACKGROUND: The advent of immune checkpoint inhibitors has dramatically changed the treatment landscape of many different tumor types. In the clinical routine, humanized antibodies against the immune checkpoints cytotoxic T‑lymphocyte associated protein 4 (CTLA-4) and programmed cell death 1/programmed cell death ligand 1 (PD1/PD-L1) are generally applied. OBJECTIVE: This article provides an overview of the treatment landscape with immune checkpoint inhibitors, especially for solid tumors in oncology. MATERIAL AND METHODS: Description and discussion of recent trial results as well as current treatment recommendations and treatment approval indications. RESULTS: In the clinical routine seven different immune checkpoint inhibitors are applied in oncology: one anti-CTLA‑4 antibody, three anti-PD1 antibodies and three anti-PD-L1 antibodies. On the US market FDA approval for 17 different tumor entities and one agnostic indication (tumors with mismatch repair mechanism deficiency/high microsatellite instability). Long-term remission can be achieved for ca. two thirds of patients with tumor response. CONCLUSION: Clinical benefits for only a part of patients treated with immune checkpoint inhibitors. The understanding of primary and secondary mechanisms of resistance to immune checkpoint inhibitors has just begun to evolve. Combination strategies of immune checkpoint inhibitors with e.g. chemotherapy, new immune checkpoint inhibitors (e.g. anti-LAG3 antibody) or targeted therapies (e.g. CDK4/6, PARP inhibitors) to improve efficacy are under clinical investigation. Reliable and predictive biomarkers are urgently needed.

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