Prospective validation of a biomarker-driven response prediction model to romiplostim in lower-risk myelodysplastic neoplasms - results of the EUROPE trial by EMSCO.

Autor: Kubasch AS; Department of Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany.; German MDS Study Group (D-MDS), Leipzig, Germany.; The European Myelodysplastic Neoplasms Cooperative Group (EMSCO), Leipzig, Germany., Giagounidis A; German MDS Study Group (D-MDS), Leipzig, Germany.; The European Myelodysplastic Neoplasms Cooperative Group (EMSCO), Leipzig, Germany.; Department of Oncology, Hematology and Palliative Care, Marien Hospital, Düsseldorf, Germany., Metzgeroth G; Department of Hematology and Oncology, University Medical Centre, Mannheim, Germany., Jonasova A; 1st Medical Department - Hematology, General Hospital, Prague, Czech Republic., Herbst R; Medizinische Klinik III, Klinikum Chemnitz, Chemnitz, Germany., Diaz JMT; Department of Hematology and Oncology, CHU de Poitiers, Poitiers, France., De Renzis B; Service d'Hématologie Clinique Adulte, Clermont Ferrand, France., Götze KS; German MDS Study Group (D-MDS), Leipzig, Germany.; The European Myelodysplastic Neoplasms Cooperative Group (EMSCO), Leipzig, Germany.; Department of Medicine III, Technical University of Munich, Munich, Germany., Huetter-Kroenke ML; Department of Hematology, Oncology, and Tumor Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Gourin MP; CHU Limoges, Limoges, France., Slama B; Service d'Hématologie, Centre Hospitalier d'Avignon, Avignon, France., Dimicoli-Salazar S; University Hospital Bordeaux, Pessac, France., Cony-Makhoul P; Centre Hospitalier Annecy-Genevois, Pringy, France., Laribi K; Centre Hospitalier Du Mans, Le Mans, France., Park S; Department of Hematology, CHU Grenoble, Grenoble, France., Jersemann K; GWT-TUD GmbH, Dresden, Germany., Schipp D; DS-Statistics, Rosenthal-Bielatal, Germany., Metzeler KH; Department of Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany.; German MDS Study Group (D-MDS), Leipzig, Germany.; The European Myelodysplastic Neoplasms Cooperative Group (EMSCO), Leipzig, Germany., Tiebel O; Institute of Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technical University Dresden, Dresden, Germany., Sockel K; German MDS Study Group (D-MDS), Leipzig, Germany.; The European Myelodysplastic Neoplasms Cooperative Group (EMSCO), Leipzig, Germany.; Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany., Gloaguen S; Department of Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany.; German MDS Study Group (D-MDS), Leipzig, Germany.; The European Myelodysplastic Neoplasms Cooperative Group (EMSCO), Leipzig, Germany.; GWT-TUD GmbH, Dresden, Germany., Mies A; Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany., Chermat F; Groupe Francophone des Myélodysplasies, Paris, France., Thiede C; Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany., Sapena R; Groupe Francophone des Myélodysplasies, Paris, France., Schlenk RF; Department of Internal Medicine V, University Hospital of Heidelberg, Heidelberg, Germany.; NCT-clinical Trials Office, German Cancer Research Center, Heidelberg, Germany., Fenaux P; The European Myelodysplastic Neoplasms Cooperative Group (EMSCO), Leipzig, Germany.; Groupe Francophone des Myélodysplasies, Paris, France.; Hématologie Clinique, Hôpital Saint-Louis, Paris, France., Platzbecker U; Department of Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany. uwe.platzbecker@medizin.uni-leipzig.de.; German MDS Study Group (D-MDS), Leipzig, Germany. uwe.platzbecker@medizin.uni-leipzig.de.; The European Myelodysplastic Neoplasms Cooperative Group (EMSCO), Leipzig, Germany. uwe.platzbecker@medizin.uni-leipzig.de., Adès L; The European Myelodysplastic Neoplasms Cooperative Group (EMSCO), Leipzig, Germany.; Groupe Francophone des Myélodysplasies, Paris, France.; Hématologie Clinique, Hôpital Saint-Louis, Paris, France.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2022 Oct; Vol. 36 (10), pp. 2519-2527. Date of Electronic Publication: 2022 Sep 07.
DOI: 10.1038/s41375-022-01669-z
Abstrakt: The EUROPE phase 2 trial investigated the predictive value of biomarkers on the clinical efficacy of single agent romiplostim (ROM) treatment in patients with lower-risk myelodysplastic neoplasms (LR-MDS) and thrombocytopenia within the 'European Myelodysplastic Neoplasms Cooperative Group' (EMSCO) network. A total of 77 patients with LR-MDS and a median platelet count of 25/nl were included, all patients received ROM at a starting dose of 750 μg by SC injection weekly. Thirty-two patients (42%) achieved a hematologic improvement of platelets (HI-P) with a median duration of 340 days. Neutrophil (HI-N) and erythroid (HI-E) responses were observed in three (4%) and seven (9%) patients, respectively. We could not confirm previous reports that HI-P correlated with baseline endogenous thrombopoietin levels and platelet transfusion history, but SRSF2 mutation status and hemoglobin levels at baseline were significantly linked to HI-P. Sequential analysis of variant allelic frequency of mutations like SRSF2 did not reveal an impact of ROM on clonal evolution in both responders and non-responders. In summary, our study confirms the safety and efficacy of ROM in LR-MDS patients and may allow to better define subgroups of patients with a high likelihood of response.
(© 2022. The Author(s).)
Databáze: MEDLINE
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