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. 2022 Oct;36(10):2519-2527.
doi: 10.1038/s41375-022-01669-z. Epub 2022 Sep 7.

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

Anne Sophie Kubasch  1   2   3 , Aristoteles Giagounidis  2   3   4 , Georgia Metzgeroth  5 , Anna Jonasova  6 , Regina Herbst  7 , Jose Miguel Torregrosa Diaz  8 , Benoit De Renzis  9 , Katharina S Götze  2   3   10 , Marie-Luise Huetter-Kroenke  11 , Marie-Pierre Gourin  12 , Borhane Slama  13 , Sophie Dimicoli-Salazar  14 , Pascale Cony-Makhoul  15 , Kamel Laribi  16 , Sophie Park  17 , Katja Jersemann  18 , Dorothea Schipp  19 , Klaus H Metzeler  1   2   3 , Oliver Tiebel  20 , Katja Sockel  2   3   21 , Silke Gloaguen  1   2   3   18 , Anna Mies  21 , Fatiha Chermat  22 , Christian Thiede  21 , Rosa Sapena  22 , Richard F Schlenk  23   24 , Pierre Fenaux  3   22   25 , Uwe Platzbecker #  26   27   28 , Lionel Adès #  3   22   25
Affiliations

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

Anne Sophie Kubasch et al. Leukemia. 2022 Oct.

Abstract

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.

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Conflict of interest statement

The EUROPE study was partially supported by Amgen GmbH. UP, Research funding: Janssen Pharmaceuticals. Consultancy and Honoraria: Novartis, Abbvie, Celgene. AG, Research funding: Janssen Pharmaceuticals. PF: Research funding: Janssen Pharmaceuticals. RS, Honoraria and Research Funding: Teva Pharmaceutical Industries. CT, Employment and Equity Ownership: AgenDix GmbH, Consultancy, Honoraria, Research Funding and Speakers Bureau: Novartis, Honararia: Daiichi Sankyo. LA: Research funding: Janssen Pharmaceuticals. Consultancy and Honoraria: Celgene, Novartis, Takeda Jazz, Abbvie. ASK: Research funding: Janssen Pharmaceuticals. Consultancy and Honoraria: Novartis, Janssen Pharmaceuticals., Takeda. The other authors declare no relevant conflicts of interests.

Figures

Fig. 1
Fig. 1. Study design of the EUROPE trial.
After screening and eligibility check, patients were assigned into two different cohorts depending on their endogenous TPO-level and previous platelet transfusion events (PTE).
Fig. 2
Fig. 2. Mutational landscape of patients included in the EUROPE trial.
A SRSF2 allelic burden and median platelet count in responders vs. non-responders. The course of median SRSF2 allelic burden and median platelet counts were compared at screening and after 16 weeks (primary endpoint, pEP) of ROM treatment. B Course of variant allelic burden in the EUROPE trial. Pattern of variant allelic burden at screening and after 16 weeks (pEP) of ROM treatment. No clinically relevant changes in clonal burden were observed in responders compared to non-responders.
Fig. 3
Fig. 3. Response prediction model to Romiplostim based on the results of the EUROPE trial.
The newly developed response prediction model contains the SRSF2 mutation status in combination with platelet count and hemoglobin level (threshold 11.4 g/dl).
See this image and copyright information in PMC

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