Search

Purpose: Currently, there are no robust biomarkers that predict immunotherapy outcomes in metastatic melanoma. We sought to build multivariable predictive models for response and survival to anti-programmed cell death protein 1 (anti-PD-1) monotherapy or in combination with anticytotoxic T-cell lymphocyte-4 (ipilimumab [IPI]; anti-PD-1 ± IPI) by including routine clinical data available at the point of treatment initiation., Methods: One thousand six hundred forty-four patients with metastatic melanoma treated with anti-PD-1 ± IPI at 16 centers from Australia, the United States, and Europe were included. Demographics, disease characteristics, and baseline blood parameters were analyzed. The end points of this study were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The final predictive models for ORR, PFS, and OS were determined through penalized regression methodology (least absolute shrinkage and selection operator method) to select the most significant predictors for all three outcomes (discovery cohort, N = 633). Each model was validated internally and externally in two independent cohorts (validation-1 [N = 419] and validation-2 [N = 592]) and nomograms were created., Results: The final model for predicting ORR (area under the curve [AUC] = 0.71) in immunotherapy-treated patients included the following clinical parameters: Eastern Cooperative Oncology Group Performance Status, presence/absence of liver and lung metastases, serum lactate dehydrogenase, blood neutrophil-lymphocyte ratio, therapy (monotherapy/combination), and line of treatment. The final predictive models for PFS (AUC = 0.68) and OS (AUC = 0.77) included the same variables as those in the ORR model (except for presence/absence of lung metastases), and included presence/absence of brain metastases and blood hemoglobin. Nomogram calculators were developed from the clinical models to predict outcomes for patients with metastatic melanoma treated with anti-PD-1 ± IPI., Conclusion: Newly developed combinations of routinely collected baseline clinical factors predict the response and survival outcomes of patients with metastatic melanoma treated with immunotherapy and may serve as valuable tools for clinical decision making., Competing Interests: Inês Pires da SilvaConsulting or Advisory Role: MSDSpeakers' Bureau: Roche, Novartis, Bristol Myers SquibbTravel, Accommodations, Expenses: Roche, Bristol Myers Squibb Jennifer L. McQuadeHonoraria: Merck, Bristol Myers Squibb, RocheConsulting or Advisory Role: Bristol Myers Squibb, Roche Pharma AGTravel, Accommodations, Expenses: Merck Selma UgurelHonoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Roche, Novartis, Merck SeronoConsulting or Advisory Role: Bristol Myers Squibb, Roche, Merck SeronoResearch Funding: Bristol Myers Squibb (Inst), Merck Serono (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, Merck Sharp & Dohme, Roche, Novartis, Pierre Fabre Rudolf HerbstEmployment: Helios Kliniken Jochen UtikalStock and Other Ownership Interests: BioNTech, Moderna Therapeutics, Pfizer, Merck, SanofiHonoraria: Bristol Myers Squibb, Novartis, MSD Oncology, Roche, Pierre Fabre, SanofiConsulting or Advisory Role: Bristol Myers Squibb, Roche, MSD Oncology, Novartis, Pierre Fabre, Amgen, SanofiResearch Funding: Apogenix (Inst), Noxxon Pharma (Inst), Elsalys Biotech (Inst), TILT Biotherapeutics (Inst)Travel, Accommodations, Expenses: MSD Oncology, Roche, Novartis, Pierre Fabre, Bristol Myers Squibb, Amgen, Sanofi Claudia PföhlerHonoraria: Bristol Myers Squibb, Novartis, Roche, MSD, Merck Serono, Sun Pharma, Amgen, AbbVieConsulting or Advisory Role: Bristol Myers Squibb Foundation, Novartis, MSD, Roche, Sanofi, Allergy Therapeutics, Merck SeronoTravel, Accommodations, Expenses: Bristol Myers Squibb, Novartis, MSD, Roche, Pierre Fabre, Celgene, AbbVie, Merck Serono Patrick TerheydenHonoraria: Bristol Myers Squibb, Novartis, Roche, CureVac, Merck Serono, MSD OncologyConsulting or Advisory Role: Bristol Myers Squibb, Novartis, Pierre Fabre, Roche, Sanofi, Merck KGaA, 4SC, AlmirallTravel, Accommodations, Expenses: Bristol Myers Squibb, Pierre Fabre Michael WeichenthalHonoraria: Merck Sharp & Dohme, Roche, Novartis, Bristol Myers Squibb, SanofiConsulting or Advisory Role: Merck Sharp & Dohme, Roche, Novartis, Bristol Myers Squibb, Sun Pharma, Sanofi, Pierre FabreResearch Funding: Merck Sharp & Dohme (Inst), Millennium (Inst), Bristol Myers Squibb (Inst), Johnson & Johnson (Inst), Novartis (Inst) Ralf GutzmerHonoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Roche/Genentech, Novartis, Merck Serono, Almirall Hermal GmbH, Amgen, Sun Pharma, Pierre Fabre, Sanofi/Regeneron, ImmunocoreConsulting or Advisory Role: Bristol Myers Squibb, Merck Sharp & Dohme, Roche/Genentech, Novartis, Almirall Hermal GmbH, 4SC, Amgen, Pierre Fabre, Merck Serono, Sun Pharma, Sanofi, ImmunocoreResearch Funding: Pfizer (Inst), Novartis (Inst), Johnson & Johnson (Inst), Amgen (Inst), Merck Serono (Inst), Sun Pharma (Inst), Sanofi (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, Roche, Merck Serono, Pierre Fabre, Sun Pharma Peter MohrHonoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Roche/Genentech, Novartis, Amgen, Pierre Fabre, Merck, SanofiConsulting or Advisory Role: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Amgen, Roche, Merck, Pierre Fabre, SanofiSpeakers' Bureau: Novartis, Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Amgen, SanofiResearch Funding: Merck Sharp & Dohme (Inst), Bristol Myers Squibb (Inst), Novartis (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Amgen, Roche, Sun Pharma, Sanofi Jessica L. SmithHonoraria: Pierre FabreTravel, Accommodations, Expenses: MSD Oncology Richard A. ScolyerEmployment: Royal Prince Alfred HospitalHonoraria: GlaxoSmithKline, Harvard Medical School, Wake Forest School of MedicineConsulting or Advisory Role: Bristol Myers Squibb GesmbH (Austria), Bristol Myers Squibb SA (Switzerland), GlaxoSmithKline, Merck Sharp & Dohme, NeraCare GmbH, Novartis Australia, Amgen, Myriad Genetics, MSD Sharp & Dohme (Australia) Pty Limited, Novartis, QBiotics, Provectus Biopharmaceuticals Australia, Evaxion BioTech A/S, Novartis Pharmaceuticals Australia Pty Limited, RocheResearch Funding: The Ainsworth Foundation (Inst), National Health and Medical Research Council, Melanoma Research Alliance (MRA) GrantTravel, Accommodations, Expenses: Bristol Myers Squibb, Novartis AustraliaUncompensated Relationships: Melanoma Institute Australia Ana M. AranceConsulting or Advisory Role: BMS, Roche, Novartis, Pierre Fabre, MSD, Merck, SanofiSpeakers' Bureau: Pierre Fabre, Novartis, MSD, BMS, Roche, Merck, SanofiResearch Funding: Pierre Fabre, Novartis, Roche, BMS, MSD, Merck, Sanofi, AmgenTravel, Accommodations, Expenses: BMS, MSD, Novartis, Pierre Fabre, Roche, Merck, Sanofi Lisa PickeringConsulting or Advisory Role: Pfizer, Ipsen, BMS, Eisai, MSD Oncology, NovartisSpeakers' Bureau: Pfizer, BMSResearch Funding: NIHR (Inst), Rosetrees Trust (Inst), Kidney and melanoma cancer fund of RMH charity (Inst) James LarkinHonoraria: Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Novartis, Roche/Genentech, Incyte, iOnctura, Merck Serono, Eisai, Dynavax Technologies, Cancer Research UK, touchIME, touchEXPERTSConsulting or Advisory Role: Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Novartis, Boston Biomedical, Incyte, iOnctura, Iovance Biotherapeutics, Immunocore, YKT Corporation, Apple Tree PartnersResearch Funding: Pfizer (Inst), Novartis (Inst), MSD (Inst), Bristol Myers Squibb (Inst), Achilles Therapeutics (Inst), Roche (Inst), Nektar (Inst), Covance (Inst), Immunocore (Inst), AVEO (Inst), Pharmacyclics (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, Pfizer, Novartis, Roche/Genentech, AstraZeneca, Incyte, GlaxoSmithKline, Pierre Fabre, Merck Serono, iOnctura, British Uro-Oncology Group (BUG), ESMO, National Cancer Research Institute (NCRI), EUSA Pharma, Syneos Health, Kidney Cancer Association, Bioevents, MedConcept, RV Mais Paul LoriganHonoraria: Novartis, Pierre Fabre, Merck, BMS, MSD, NeraCare GmbH, Amgen, Roche, Oncology Education, NektarConsulting or Advisory Role: Merck Sharp & Dohme, Bristol Myers Squibb, Amgen, Pierre Fabre, Novartis, NektarSpeakers' Bureau: Merck Sharp & Dohme, Novartis, Bristol Myers Squibb, Pierre FabreResearch Funding: BMS, Pierre FabreTravel, Accommodations, Expenses: Merck Sharp & Dohme, Bristol Myers Squibb Christian U. BlankStock and Other Ownership Interests: Uniti Cars, ImmageneConsulting or Advisory Role: Roche/Genentech (Inst), MSD Oncology (Inst), Bristol Myers Squibb (Inst), Novartis (Inst), GlaxoSmithKline (Inst), Pfizer (Inst), AstraZeneca (Inst), Lilly (Inst), Pierre Fabre (Inst), GenMab (Inst), Third Rock VenturesResearch Funding: Bristol Myers Squibb (Inst), Novartis (Inst), NanoString Technologies (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb Dirk SchadendorfHonoraria: Roche/Genentech, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Immunocore, Merck Serono, Array BioPharma, Pfizer, Pierre Fabre, Philogen, Regeneron, 4SC, Sanofi/Regeneron, NeraCare GmbH, Sun Pharma, InflarxGmbH, Ultimovacs, SandozConsulting or Advisory Role: Roche/Genentech, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, 4SC, Pierre Fabre, Sanofi/Regeneron, NektarSpeakers' Bureau: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi/Regeneron, Merck KGaAResearch Funding: Bristol Myers Squibb (Inst), Novartis (Inst), Roche (Inst), MSD Oncology (Inst), Array BioPharma/Pfizer (Inst)Travel, Accommodations, Expenses: Roche/Genentech, Bristol Myers Squibb, Merck Serono, Novartis, Merck Sharp & Dohme, Pierre Fabre, Sanofi/Regeneron Michael A. DaviesConsulting or Advisory Role: Genentech/Roche, Novartis, Bristol Myers Squibb, NanoString Technologies, Array BioPharma, Apexigen, ABM Therapeutics, Pfizer, EisaiResearch Funding: GlaxoSmithKline (Inst), Genentech/Roche (Inst), AstraZeneca (Inst), Merck (Inst), Oncothyreon (Inst), Myriad Genetics (Inst), Sanofi (Inst), Pfizer (Inst) Matteo S. CarlinoHonoraria: Bristol Myers Squibb, MSD, NovartisConsulting or Advisory Role: Bristol Myers Squibb, MSD, Amgen, Novartis, Pierre Fabre, Roche, IDEAYA Biosciences, Sanofi, Merck Serono, Regeneron, QBiotics, Nektar, Eisai, OncoSec Douglas B. JohnsonConsulting or Advisory Role: Bristol Myers Squibb, Merck, Novartis, Janssen, Iovance Biotherapeutics, Catalyst Pharmaceuticals, Oncosec, Pfizer, Mosaic ImmunoEngineering, TargovaxResearch Funding: Incyte, Bristol Myers SquibbPatents, Royalties, Other Intellectual Property: Intellectual property and patents pending surrounding use of MHC-II and response to immune therapy Georgina V. LongHonoraria: BMS, Pierre FabreConsulting or Advisory Role: Aduro Biotech, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Hexal, Highlight Therapeutics, Merck Sharpe & Dohme, Novartis, OncoSec, Pierre Fabre, QBiotics, Regeneron, SkylineDx, Specialised Therapeutics, Array BioPharma, Evaxion Biotech A/S, Evaxion Biotech A/S, SkylineDX B.V Alexander M. MenziesConsulting or Advisory Role: MSD Oncology, Novartis, Pierre Fabre, Bristol Myers Squibb, Roche, QBioticsNo other potential conflicts of interest were reported.