Treatment Resistance Risk in Patients with Newly Diagnosed Multiple Myeloma Is Associated with Blood Hypercoagulability: The ROADMAP-MM Study
Grigorios T. Gerotziafas,
Despina Fotiou,
Theodoros N. Sergentanis,
Loula Papageorgiou,
Jawed Fareed,
Anna Falanga,
Michèle Sabbah,
Laurent Garderet,
Evangelos Terpos,
Ismail Elalamy,
Patrick Van Dreden,
Meletios A. Dimopoulos
Affiliations
Grigorios T. Gerotziafas
Research Team “Cancer-Hemostasis-Angiogenesis” Research Group “Cancer Biology and Therapeutics”, Centre de Recherche Saint Antoine (CRSA), Institut Universitaire de Cancérologie, Faculty of Medicine, Sorbonne University, 75012 Paris, France
Despina Fotiou
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
Theodoros N. Sergentanis
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
Loula Papageorgiou
Research Team “Cancer-Hemostasis-Angiogenesis” Research Group “Cancer Biology and Therapeutics”, Centre de Recherche Saint Antoine (CRSA), Institut Universitaire de Cancérologie, Faculty of Medicine, Sorbonne University, 75012 Paris, France
Jawed Fareed
Department of Pathology and Laboratory Medicine, Loyola University Medical Center, Maywood, IL 60153, USA
Anna Falanga
Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, School of Medicine, University of Milan Bicocca, 24127 Bergamo, Italy
Michèle Sabbah
Department of Thrombosis and Haemostasis, Service d’Hématologie Biologique DMU BioGen, Faculté de Médecine Sorbonne, Hôpital Tenon, Hôpitaux Universitaires de l’Est Parisien, Assistance Publique Hôpitaux de Paris, 75020 Paris, France
Laurent Garderet
Department of Hematology and Cellular Therapy, Hospital Hospital-Pitié Salpêtrière, 75013 Paris, France
Evangelos Terpos
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
Ismail Elalamy
Research Team “Cancer-Hemostasis-Angiogenesis” Research Group “Cancer Biology and Therapeutics”, Centre de Recherche Saint Antoine (CRSA), Institut Universitaire de Cancérologie, Faculty of Medicine, Sorbonne University, 75012 Paris, France
Patrick Van Dreden
Research Team “Cancer-Hemostasis-Angiogenesis” Research Group “Cancer Biology and Therapeutics”, Centre de Recherche Saint Antoine (CRSA), Institut Universitaire de Cancérologie, Faculty of Medicine, Sorbonne University, 75012 Paris, France
Meletios A. Dimopoulos
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
Biomarkers of hypercoagulability are potential candidates for the evaluation of risk for primary treatment resistance in patients with newly diagnosed multiple myeloma (NDMM). This study aimed to identify the most clinically relevant biomarkers for the evaluation of treatment-resistance risk. NDMM patients (n = 144) were enrolled prior to treatment initiation. Response to treatment was assessed at 3 months. STA-Procoag-PPL®, factor VIIa factor V, antithrombin, fibrin monomers, soluble thrombomodulin (TM), free TFPI, D-Dimer, P-selectin, heparanase, and thrombin generation (Calibrated Automated Thrombogram® and PPP-Reagent®) were measured. In total, 23% (n = 33) of the patients showed a poor response/resistance to treatment (defined as stable disease, minor response, progressive disease). Poor response/treatment resistance was associated with longer Procoag-PPL® clotting time, higher Peak of thrombin, and higher D-Dimer levels. These biomarkers were included in a prognostic model derived via multivariate analysis. The model had 84% sensitivity and 59% specificity to identify patients at high risk of treatment resistance. The AUC of the ROC analysis for the model was 0.75. In conclusion, Procoag-PPL®, D-Dimer, and Peak of thrombin generation are clinically relevant for the identification of NDMM patients at risk for poor response to antimyeloma treatment. A prospective multicenter study is necessary for the validation of this new approach.
