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Review
. 2021 Jul;42(4):380-390.
doi: 10.1007/s00292-021-00939-4. Epub 2021 May 6.

[Predictive diagnostics for checkpoint inhibitors]

[Article in German]
Affiliations
Review

[Predictive diagnostics for checkpoint inhibitors]

[Article in German]
Hans-Ulrich Schildhaus et al. Pathologe. 2021 Jul.

Abstract

Checkpoint inhibitors have revolutionized oncological treatment in many cancers and added a new immuno-oncological treatment pillar to the medicinal arsenal of conventional and molecularly targeted therapies. In monotherapy and in combination therapies, however, not all patients respond equally well, even in generally responsive tumor entities. Therefore, since the introduction of these therapies, a major focus has been the research on and implementation of predictive markers for patient selection. The first established biomarker, the expression of the target molecule PD-L1, has found its way into routine diagnostics in a large number of unfortunately very divergent diagnostic constellations in multiple entities. In addition, some molecular predictors, including the measurement of microsatellite instability and tumor mutational burden, have also been suggested and in some cases are already implemented into routine diagnostics. Additional molecular parameters have been proposed but most of them have not yet found their way into routine patient care. This review article discusses the current status and recent developments in the field of diagnostic response predictors in the context of an immune checkpoint blockade.

Checkpointinhibitoren haben in vielen Entitäten die onkologische Behandlung revolutioniert und dem etablierten medikamentösen Arsenal in der Onkologie eine neue, sehr mächtige immunonkologische Behandlungsmodalität zur Seite gestellt. In Mono- und auch in Kombinationstherapien sprechen jedoch selbst in grundsätzlich responsiven Entitäten nicht alle Patienten gleichermaßen gut an. Daher liegt seit Einführung dieser Therapien ein wesentlicher Fokus auch auf der Erforschung und Implementierung prädiktiver Marker zur Patientenselektion. Der erste zulassungsrelevante Biomarker, die Expression des Zielmoleküls PD-L1, hat inzwischen in einer Vielzahl leider sehr divergenter diagnostischer Konstellationen in multiplen Entitäten Einzug in die Routinediagnostik gehalten. Ebenfalls erforscht und teilweise auch bereits in unterschiedlichem Maße implementiert wurden darüber hinaus einige molekulare Prädiktoren, inklusive der Messung von Mikrosatelliteninstabilität und Tumormutationslast. Einige weitere Parameter wurden vorgeschlagen, haben jedoch noch nicht den Weg in die Routineanwendung gefunden. In diesem Übersichtsartikel werden der aktuelle Stand und neue Entwicklungen zur Prädiktion im Kontext einer Immuncheckpointblockade diskutiert.

Keywords: Immunooncology; Microsatellite instability; PD-L1; Patient selection; Tumor mutational burden.

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References

Literatur

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