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DOI: 10.1055/a-1952-1233
Profound tumor response to combined CTLA-4 and PD-1 inhibition in systemic fourth line therapy observed in a patient with hepatocellular carcinoma harboring SETD2 and LRP1B mutations
Profundes Tumoransprechen unter kombinierter CTLA-4 und PD-1 Inhibition in systemischer Viertlinie bei einem Patienten mit Hepatozellulärem Karzinom und Nachweis von SETD2 und LRP1B Mutationen
Abstract
Immunotherapy has become the standard of care in advanced HCC but is only approved in first- or second-line treatment. We report a patient with HCC refractory to several lines of tyrosine kinase inhibitors, who was treated with Ipilimumab and Nivolumab (Ipi/Nivo) as the fourth line. The tumor responded profoundly to Ipi/Nivo. Established biomarker-predicting responses to immunotherapy, such as a high PD-L1 staining, a high combined-positive score, microsatellite instability or a high tumor mutational burden, were not detected. Potential negative predictive markers for response to immunotherapy such as CTNNB1 and TERT were present. This constellation puts the spotlight on two mutations observed here in the SET domain-containing 2 (SETD2) and low-density lipoprotein receptor-related protein 1b (LRP1B) genes, which may explain the outstanding response. Our case demonstrates that immunotherapy can be efficient in a late-line scenario, resulting in long-term survival. Further studies should prospectively evaluate the value of SETD2 and LRP1B alterations as predictors for the success of immunotherapy in HCC.
Zusammenfassung
Die Immuntherapie wurde der Therapiestandard für die Behandlung des fortgeschrittenen HCC, ist allerdings nur in der Erst- oder Zweitlinie zugelassen. Wir berichten hier über einen Patienten mit HCC, der in einer TKI-refraktären Situation mit Ipi/Nivo in der Viertlinie therapiert wurde. Der Tumor sprach profunde auf die Therapie mit Ipi/Nivo an. Etablierte Biomarker, die ein Ansprechen auf eine Immuntherapie voraussagen können, wie eine hohe PD-L1-Expression, ein hoher Combined-Positive-Score, eine Mikrosatelliteninstabilität oder eine hohe Tumormutationslast wurden nicht detektiert. Potenziell negative prädiktive Marker, wie CTNNB1 und TERT-Mutationen lagen vor. Diese Konstellation richtet das Augenmerk auf 2 nachgewiesene Mutationen in den SETD2- und LRP1B-Genen, welche das Ansprechen erklären könnten. Dieser Fallbericht demonstriert, dass die Anwendung einer Immuntherapie auch in späten Therapielinien effektiv sein kann und ein Langzeitüberleben erreicht werden kann. Weitere Studien sollten prospektiv die Wertigkeit von Alterationen im SETD2 und LRP1B als Prädiktoren für einen Therapieerfolg einer Immuntherapie im HCC untersuchen.
Publication History
Received: 26 August 2022
Accepted: 27 September 2022
Article published online:
15 November 2022
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