Publikation: Zeitschriftenartikel

Outcome of melanoma patients with elevated LDH treated with first-line targeted therapy or PD-1-based immune checkpoint inhibition

Grunddaten
Abstract
Autoren
Einrichtung

Grunddaten

Titel	Outcome of melanoma patients with elevated LDH treated with first-line targeted therapy or PD-1-based immune checkpoint inhibition
Erscheinungsjahr	2021
Seiten (von – bis)	61 – 75
Band	148
Jahr	2021
Publikationsform	Elektronische Ressource
Publikationsart	Zeitschriftenartikel
Sprache	Englisch
DOI	10.1016/j.ejca.2021.01.034
Letzte Änderung	23.02.2022 06:02:24
Bearbeitungsstatus	durch UB Rostock abschließend validiert
Dauerhafte URL	http://purl.uni-rostock.de/fodb/pub/67521
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Abstract

Background - Elevated lactate dehydrogenase (LDH) is a known predictive and prognostic factor for a poor outcome in patients with metastatic melanoma. It is unclear whether first-line targeted therapy (TT) or immune checkpoint inhibition (ICI) is more beneficial in melanoma patients with elevated LDH because prospective studies in this area are lacking. - Methods - This multicentre retrospective cohort study was conducted at 25 melanoma centres worldwide to analyse progression-free survival (PFS) and overall survival (OS) among melanoma patients with elevated LDH. The role of confounders was addressed by using inverse probability of treatment weighting. - Results - Among 173 BRAFV600-mutant patients, PFS at 12 months in the TT group was 22% compared with 52% in the combined anti-PD-1 and anti-CTLA-4 group (HR 0.6, 95% CI 0.4-1.0, p = 0.07) and 18% in the anti-PD-1 monotherapy group (HR 1.8, 95% CI 1.2-2.8, p = 0.003). Twelve months' OS was 48% in the TT group compared with 83% in the combined anti-PD-1 and anti-CTLA-4 group (HR 0.5, 95% CI 0.3-1.0, p = 0.03) and 50% in the anti-PD-1 monotherapy group (HR 1.2, 95% CI 0.8-2.0, p = 0.37). The ORR in the TT group was 63%, compared with 55% and 20% in the combined anti-PD-1 and anti-CTLA-4 and anti-PD-1 monotherapy group, respectively. Among 314 patients receiving ICI first-line, PFS at 12 months was 33% in the anti-PD-1 group versus 38% in the combined anti-PD-1 and anti-CTLA-4 group (HR 0.8, 95% CI 0.6-1.0; p = 0.07). OS at 12 months was 54% in the anti-PD-1 group versus 66% in the combined ICI group (HR 0.7, 95% CI 0.5-1.0; p = 0.03). The ORR was 30% in the anti-PD-1 monotherapy group and 43% in the combined anti-PD-1 and anti-CTLA-4 group. Results from multivariate analysis confirmed the absence of qualitative confounding. - Conclusions - Among BRAF-mutant patients with elevated LDH, combined anti-PD-1 and anti-CTLA-4 blockade seems to be associated with prolonged OS compared with first-line TT. Among patients receiving ICI as a first-line treatment, OS appears to be longer for the combination of anti-PD-1 and anti-CTLA-4 than for anti-PD-1 alone.

Autoren

Knispel, Sarah

Gassenmaier, Maximilian

Menzies, Alexander

Loquai, Carmen

Johnson, Douglas B.

Franklin, Cindy

Gutzmer, Ralf

Hassel, Jessica C.

Weishaupt, Carsten

Eigentler, Thomas

Schilling, Bastian

Schummer, Patrick

Sirokay, Judith

Kiecker, Felix

Owen, Carina N.

Fleischer, Maria I.

Cann, Christopher

Kähler, Katharina C.

Mohr, Peter

Bluhm, Leonie

Niebel, Dennis

Thoms, Kai-Martin

Goldinger, Simone M.

Reinhardt, Lydia

Meier, Friedegund

Berking, Carola

Reinhard, Raphael

Susok, Laura

Ascierto, Paolo

Drexler, Konstantin Maximilian

Pföhler, Claudia Ursula

Tietze, Julia K.

Heinzerling, Lucie

Livingstone, Elisabeth

Ugurel, Selma

Long, Georgina

Stang, Andreas

Schadendorf, Dirk

Zimmer, Lisa

Einrichtung

UMR/Klinik und Poliklinik für Dermatologie und Venerologie (DUK)