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

Autor: Knispel S; Department of Dermatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Gassenmaier M; Department of Dermatology, University Hospital Tübingen, Tübingen, Germany., Menzies AM; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, Australia., Loquai C; Department of Dermatology, University Medical Center Mainz, Mainz, Germany., Johnson DB; Vanderbilt University Medical Center, Nashville, USA., Franklin C; Department of Dermatology and Venereology, Skin Cancer Center at the Center of Integrated Oncology (CIO) Köln Bonn, University Hospital of Cologne, Cologne, Germany., Gutzmer R; Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany., Hassel JC; Skin Cancer Center, Department of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany., Weishaupt C; Department of Dermatology, University Hospital of Muenster, Muenster, Germany., Eigentler T; Department of Dermatology, University Hospital Tübingen, Tübingen, Germany., Schilling B; Department of Dermatology, University Hospital Würzburg, Würzburg, Germany., Schummer P; Department of Dermatology, University Hospital Würzburg, Würzburg, Germany., Sirokay J; Department of Dermatology, University Hospital Bonn, Bonn, Germany., Kiecker F; Department of Dermatology, University Hospital Charité Berlin, Berlin, Germany., Owen CN; Melanoma Institute Australia, The University of Sydney, Sydney, Australia., Fleischer MI; Department of Dermatology, University Medical Center Mainz, Mainz, Germany., Cann C; Vanderbilt University Medical Center, Nashville, USA., Kähler KC; Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany., Mohr P; Department of Dermatology, Elbe-Klinikum Buxtehude, Buxtehude, Germany., Bluhm L; Department of Dermatology, Elbe-Klinikum Buxtehude, Buxtehude, Germany., Niebel D; Department of Dermatology, University Hospital Bonn, Bonn, Germany., Thoms KM; Department of Dermatology, University Medical Center Goettingen, Göttingen, Germany., Goldinger SM; Department of Dermatology, University Hospital Zürich, Zürich, Switzerland., Reinhardt L; Department of Dermatology, Skin Cancer Center at the National Center for Tumor Diseases, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany., Meier F; Department of Dermatology, Skin Cancer Center at the National Center for Tumor Diseases, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany., Berking C; Department of Dermatology, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen - Metropolitan Region of Nuremberg, Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Reinhard R; Skin Cancer Unit, German Cancer Research Center (DKFZ) and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Mannheim, Germany., Susok L; Department of Dermatology, St. Josef-Hospital Bochum, Bochum, Germany., Ascierto PA; Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy., Drexler K; Department of Dermatology, University Hospital Regensburg, Regensburg, Germany., Pföhler C; Department of Dermatology, Saarland University Medical School, Homburg/Saar, Germany., Tietze J; Department of Dermatology, University Hospital Rostock, Rostock, Germany., Heinzerling L; Department of Dermatology, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen - Metropolitan Region of Nuremberg, Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Livingstone E; Department of Dermatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Ugurel S; Department of Dermatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Long GV; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, Australia., Stang A; Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany., Schadendorf D; Department of Dermatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Zimmer L; Department of Dermatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. Electronic address: lisa.zimmer@uk-essen.de.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2021 May; Vol. 148, pp. 61-75. Date of Electronic Publication: 2021 Mar 15.
DOI: 10.1016/j.ejca.2021.01.034
Abstrakt: 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.
Competing Interests: Conflicts of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sarah Knispel: Travel support from Bristol-Myers Squibb and Amgen. Maximilian Gassenmaier: Consultant or Advisory Role: Novartis; Research funding: Novartis. Carmen Loquai: Advisory role/Speakers fee/Travel support: BMS, MSD, Merck, Novartis, Pierre Fabre, Sunpharma, Sanofi, Roche, Almirall Hermal, Biontech, Kyowa Kirin. Cindy Franklin: Advisory board or received honoraria of BMS and Novartis and received travel grants from BMS, Novartis and Pierre Fabre. Ralf Gutzmer: Personal Honoraria from Roche, BMS, MSD, Novartis, Amgen, Merck Serono, Almirall Hermal, SUN, Sanofi, Pierre-Fabre. Consultant or advisory role: BMS, Roche, Novartis, Almirall Hermal, MSD, Amgen, SUN, Sanofi, Pierre-Fabre, MerckSerono, Bayer, Pfizer. Research funding: Novartis, Pfizer, Johnson & Johnson, Amgen, Merck-Serono, SUN Pharma, Sanofi, all paid to the institution. Travel, accommodations, expenses: Roche, BMS, SUN, Merck-Serono, Pierre-Fabre. Bastian Schilling: Personal honoraria from Bristol-Myers Squibb, Merck Sharpe and Dome, Novartis, Pfizer/EMD Serono, Pierre Fabre and Roche; has an advisory role for Bristol-Myers Squibb, Merck Sharpe and Dome, Novartis, Pierre Fabre and Roche; and has received research funding from Bristol-Myers Squibb, Merck Sharpe and Dome, and Pierre Fabre, all paid to the institute. Andreas Stang: Speaker honoraria from Merck Serono. Selma Ugurel: Research support from Bristol-Myers Squibb and Merck Serono; speakers and advisory board honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, Merck Serono, Novartis and Roche, and Travel support from Bristol-Myers Squibb, and Merck Sharp & Dohme. Lisa Zimmer: Honoraria from Roche, BMS, MSD, Novartis, Pierre Fabre; Consultant or advisory role: BMS, Novartis, Pierre Fabre, Sunpharma, Sanofi, MSD; Research funding to institution: Novartis; Travel support: BMS, Pierre Fabre, Sanofi, Amgen, Novartis, Sunpharma. Carina N Owen: Travel support from Merck Sharp Dohme. Jessica C Hassel: Honoraria from BMS, MSD, Novartis, Roche, Pierre Fabre, Sanofi; Consultant or advisory role: MSD, Pierre Fabre, Sunpharma; Research funding: BMS; Travel support: Pierre Fabre. Friedegund Meier has received travel support or/and speaker's fees or/and advisor's honoraria by Novartis, Roche, BMS, MSD and Pierre Fabre and research funding from Novartis and Roche. Carola Berking: Honoraria from BMS, Immunocore, Merck, MSD, Novartis, Pierre Fabre, Roche, Sanofi-Aventis for consultancy and/or presentations on scientific symposia. Douglas B Johnson: Advisory boards for Array Biopharma, BMS, Iovance, Jansen, Merck and Novartis and research funding from BMS and Incyte. Elisabeth Livingstone: Intermittent advisory board relationships with Roche, BMS, Novartis, Sanofi and Actelion and has received travel grants and honoraria from Roche, BMS, MSD, Amgen, Pierre Fabre, SunPharma, Novartis, Boehringer-Ingelheim, medac. Alexander M Menzies: Advisory boards for BMS, MSD, Novartis, Roche, Pierre-Fabre, QBiotics. Simone M Goldinger: past advisory boards for BMS, MSD, Roche and Novartis. Kai-Martin Thoms: Honoraria from BMS, MSD, Roche, Novartis, Pierre Fabre, Sun Pharma, LEO, Candela; Consultant or advisory role: BMS, MSD, Roche, Novartis, Pierre Fabre, Sun Pharma, LEO; Travel support: BMS, MSD, Roche, Novartis, Pierre Fabre, LEO. Dirk Schadendorf: Has/had a consultant/advisory role in the last 2 years for Bristol-Myers Squibb (BMS), Roche-Genentech, Merck Sharp & Dohme (MSD), Array, Immunocore, InFlaRX, Nektar, Novartis, Merck Serono, Pierre Fabre, Pfizer, Philogen, Regeneron, SunPharma, Sandoz, Sanofi, Ultimovacs and 4SC. He also received research funds from Bristol-MyersSquibb, Roche, Amgen and Novartis. Travel support: BMS, Pierre Fabre, Sanofi, Nektar, Novartis, Roche, Merck Serono and Sunpharma. Dennis Niebel: Has received speakers’ honoraria or travel expense reimbursements from BMS, Novartis, GSK, Celgene and MSD. Judith Sirokay: Honoraria from Roche, BMS, MSD, Novartis, Consultant or advisory role: Novartis, MSD; Travel support: BMS, Pierre Fabre. Peter Mohr: Has/had a consultant/advisory role in the last 2 years for Amgen, Bristol-Myers Squibb (BMS), Roche-Genentech, Merck Sharp & Dohme (MSD), Novartis, Merck Serono, Pierre Fabre, Pfizer, Philogen, Sanofi. He also received research funds from Bristol-Myers Squibb, Merck Sharp & Dohme (MSD) and Novartis. Travel support: Amgen, BMS, Merck Sharp & Dohme (MSD), Pierre Fabre, Sanofi, Novartis, Roche and Sunpharma. Laura Susok: Collaboration with BMS, Novartis, Sunpharma, MSD, Roche, Pierre Fabre. Paolo Ascierto: Has/had a consultant/advisory role for Bristol-Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Array, Merck Serono, Pierre-Fabre, Incyte, Medimmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Array and travel support from MSD. Claudia Pföhler: Consultancy, speaker fees, travel grants: BMS, MSD, Merck Serono, Roche, Amgen, GSK, Novartis, Sanofi Genzyme, Pierre Fabre, LEO, UCB, Sunpharma. Clinical studies: Novartis, BMS. Lucie Heinzerling: Consultant or advisory role: Amgen, BMS, Curevac, Novartis, Pierre Fabre, Roche, Sanofi, MSD; research funding (to institution): Novartis. Patrick Schummer: honoraria: Bristol-Myers Squibb (BMS); institutional research grant: Novartis; Travel support: Novartis, Lilly and BMS. Thomas Eigentler: Has/had a consultant/advisory role in the last 2 years for Bristol-Myers Squibb (BMS), Roche-Genentech, Merck Sharp & Dohme (MSD), Novartis, Pierre Fabre, Philogen, Sanofi. He also received research funds from Bristol-Myers Squibb, Merck Sharp & Dohme (MSD) and Novartis. Katharina C. Kähler: Serves as consultant to Roche, BMS, MSD, Pierre Fabre and received travel grants and speaker fees from Roche, BMS, MSD, Amgen, Pierre Fabre and Philogen. Julia Tietze: Honoraria from Roche, BMS, MSD, Amgen, Sanofi, Travel support: Pierre Fabre, Novartis, BMS. Georgina V. Long: Is consultant advisor for Aduro Biotech Inc, Amgen Inc, Array Biopharma Inc, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Highlight Therapeutics S.L., Merck Sharpe & Dohme, Novartis Pharma AG, QBiotics Group Limited, Regeneron Pharmaceuticals Inc, SkylineDX B.V. All other authors (Felix Kiecker, Raphael Reinhard, Konstantin Drexler, Christopher Cann, Lydia Reinhardt, Carsten Weishaupt, Maria I Fleischer, Leonie Bluhm) declared to have no conflicts of interest.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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