title: Modeling combined chemo- and immunotherapy of high-grade non-Hodgkin lymphoma.
abstract: Moderate, but not massive intensification of CHOP-21 improves outcome in aggressive non-Hodgkin lymphoma. Adding immunotherapy with Rituximab was a break-through, but levels differences in chemotherapy. Ongoing trials attempt to optimize R-CHOP type regimens. We present a mathematical model of chemo-immunotherapy to explain published and aiming at predicting future trials comparing R-CHOP variants. We hypothesize that, for cure, the immune system must dominate residual tumor cells at the end of treatment. Chemotherapy reduces both tumor and immune cells. Rituximab immunotherapy boosts the immune response. We translate this reasoning into a differential equations model. Model parameters are estimated using data of randomized clinical trials in elderly patients. The model explains observed hazard ratios between treatments. It explains why too intense chemotherapy could be detrimental. The model is validated predicting six published independent studies. As an application, we varied treatment schedules and predict that current R-CHOP variants have only limited optimization potential.
authors.affiliation: a Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig , Leipzig , Germany ;|b LIFE Research Center for Civilization Diseases, University of Leipzig , Leipzig , Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Rösch
authors.affiliation: a Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig , Leipzig , Germany ;|b LIFE Research Center for Civilization Diseases, University of Leipzig , Leipzig , Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Scholz
authors.affiliation: a Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig , Leipzig , Germany ;
authors.forename: Dirk
authors.initials: D
authors.lastname: Hasenclever
mesh_terms: D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003198:Computer Simulation; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology* / Q000628:therapy*; D008962:Models, Theoretical; D060787:Neoplasm Grading; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D012307:Risk Factors; D016896:Treatment Outcome
keywords: Biomathematical model; Rituximab; chemotherapy; lymphoma