{"database":"BioModels","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Csv":["https://www.ebi.ac.uk/biomodels/model/download/MODEL2412270001?filename=CC122_PK_dose5mg_schedule5of7.csv"],"Other":["https://www.ebi.ac.uk/biomodels/model/download/MODEL2412270001?filename=12248_2021_623_MOESM3_ESM.r"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"submitter":["Abbiati Roberto Andrea"],"curationStatus":["Non-curated"],"modellingApproach":["differential equation model"],"levelVersion":["*"],"full_dataset_link":["https://www.ebi.ac.uk/biomodels/MODEL2412270001"],"isPrivate":["false"],"repository":["BioModels"],"modelFormat":["R"],"omics_type":["Models"],"tokenised_name":["Abbiati2021 Avadomide induced neutropenia model"],"publication_year":["2021"],"submissionId":["MODEL2412270001"],"publication_authors":["Abbiati Roberto Andrea, Michael Pourdehnad, Soraya Carrancio, Daniel W Pierce, Shailaja Kasibhatla, Mark McConnell, Matthew W B Trotter, Remco Loos, Remco Loos, Cristina C Santini, Alexander V Ratushny"],"first_author":["Abbiati Roberto Andrea"],"publication":["10.1208/s12248-021-00623-8,\n                            Avadomide is a cereblon E3 ligase modulator and a potent antitumor and immunomodulatory agent. Avadomide trials are challenged by neutropenia as a major adverse event and a dose-limiting toxicity. Intermittent dosing schedules supported by preclinical data provide a strategy to reduce frequency and severity of neutropenia; however, the identification of optimal dosing schedules remains a clinical challenge. Quantitative systems pharmacology (QSP) modeling offers opportunities for virtual screening of efficacy and toxicity levels produced by alternative dose and schedule regimens, thereby supporting decision-making in translational drug development. We formulated a QSP model to capture the mechanism of avadomide-induced neutropenia, which involves cereblon-mediated degradation of transcription factor Ikaros, resulting in a maturation block of the neutrophil lineage. The neutropenia model was integrated with avadomide-specific pharmacokinetic and pharmacodynamic models to capture dose-dependent effects. Additionally, we generated a disease-specific virtual patient population to represent the variability in patient characteristics and response to treatment observed for a diffuse large B-cell lymphoma trial cohort. Model utility was demonstrated by simulating the avadomide effect in the virtual population for various dosing schedules and determining the incidence of high-grade neutropenia, its duration, and the probability of recovery to low-grade neutropenia.. 5, 23.\n                            Bristol Myers Squibb, Center for Innovation and Translational Research Europe (CITRE), Seville, Spain. roberto.abbiati@bms.com."],"submitter_mail":["ro.abbiati@gmail.com"],"publication_doi":["10.1208/s12248-021-00623-8"],"submitter_affiliation":["Roche Pharma"],"name_synonyms":["neutropenic disorder, Neutropenias., neutropenia, avadomide, CC-122"],"description_synonyms":["Appointment, Networks, IPP2A2, Par1c, Systems Pharmacology, AI461847, Par-1c, number, Pierce, Network, CSV., Systematic Pharmacology, DmelCG8201, presence, avadomide, Symptoms and Signs, PHAPII, DOI, 5730420M11Rik, Publication, dPAR-1, Schedules and Appointments, Pgi, Drug-Target Networks, Finding, dPar-1, Gpi-1, Separated, Neutropenias, doi, Drug Target Network, Schedules, SET, 27C1, Divorced, TAF-I, Gpi-1r, Nlk, l(2)k06323, Gpi-1s, Patient Schedules, Phi, ipp2a2, Gpi-1t, 2pp2a, Divorces, CG10574, CC-122, Xylella fastidiosa (strain Temecula1 / ATCC 700964), DmelCG4299, neutropenic disorder, PAR-1, IGAAD, set, 2PP2A, DmelCG10574, taf-ibeta, Par-1, dSET, dSet, Systematic, Electronic Supplementary Material, CG16701, Diagnostic Findings, NK/GPI, Gpi, phapii, SIGNS SYMPTOMS, par1, Patient Appointment, CG8201, DESC, igaad, dPAR1, dPar1, StF-IT-1, dMARK, MF, Amf, CG11960, group, CG30131, CG30132, EMK, count in organism, Signs and Symptoms, mOC-X, neutropenia, I-2PP2A, Supporting Information, anon-WO0210402.19, DPAR-1, Systems, Dm I-2, Drug-Target Network, I2PP2A, Appointments, NK|GPI, Supplementary Information, NK, Separation, Org, ORG, Supplementary Material, HLA-DR-associated protein II, ensemble, DI-2, Xylella fastidiosa str. Temecula1, I-2Dm, Separations, Patient Appointments, Gpi1-r, Gpi1-s, CG4299, Gpi1-t, I-2PP1, dSET/TAF-Ibeta, l(2)27C1, 2610030F17Rik, TAF-IBETA, Patient, BcDNA:RH48823, Pharmacology, MARK, DPar1, Drug-Target, Patient Schedule, TAF-Ibeta, PAR1, Par1, Schedule, AA407739, Clinical Finding, i2pp2a, Bglap-rs1, Gpi1s"],"additional_accession":[]},"is_claimable":false,"name":"Abbiati2021_Avadomide-induced neutropenia model","description":"This is the model for avadomide-induced neutropenia published by Abbiati et al. in 2021:\nCitation: Roberto A. Abbiati, Michael Pourdehnad, Soraya Carrancio, Daniel W. Pierce, Shailaja Kasibhatla, Mark McConnell, Matthew W. B. Trotter, Remco Loos, Cristina C. Santini & Alexander V. Ratushny. Quantitative Systems Pharmacology Modeling of Avadomide-Induced Neutropenia Enables Virtual Clinical Dose and Schedule Finding Studies. AAPS J 23, 103 (2021). https://doi.org/10.1208/s12248-021-00623-8\n\nThe model reported here is equivalent to the one provided in the original publication as Supplementary Material.\n\nThe script provided contains the model equations, the initial conditions of the integration variables, and a representative set of the model parameters. It also include the instructions to execute the model in R assuming an input avadomide pharmacokinetic profile (provided as a separated csv file).","dates":{"last_modification":"2024-12-27","publication":"2025-04-07","submission":"2024-12-27"},"accession":"MODEL2412270001","cross_references":{"biomodels__db":["MODEL2412270001"],"doi":["10.1208/s12248-021-00623-8"]}}