Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes: the HOVON89 trial.

Autor: van de Loosdrecht AA; Department of Hematology, Amsterdam UMC, location VUmc, Cancer Center Amsterdam, Amsterdam, The Netherlands. a.vandeloosdrecht@amsterdamumc.nl., Cremers EMP; Department of Hematology, Amsterdam UMC, location VUmc, Cancer Center Amsterdam, Amsterdam, The Netherlands.; Department of Laboratory Medicine - Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands., Alhan C; Department of Hematology, Amsterdam UMC, location VUmc, Cancer Center Amsterdam, Amsterdam, The Netherlands., Duetz C; Department of Hematology, Amsterdam UMC, location VUmc, Cancer Center Amsterdam, Amsterdam, The Netherlands., In 't Hout FEM; Department of Laboratory Medicine - Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands., Visser-Wisselaar HA; HOVON Foundation, Rotterdam, The Netherlands., Chitu DA; HOVON Foundation, Rotterdam, The Netherlands.; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Verbrugge A; HOVON Foundation, Rotterdam, The Netherlands., Cunha SM; HOVON Foundation, Rotterdam, The Netherlands., Ossenkoppele GJ; Department of Hematology, Amsterdam UMC, location VUmc, Cancer Center Amsterdam, Amsterdam, The Netherlands., Janssen JJWM; Department of Hematology, Amsterdam UMC, location VUmc, Cancer Center Amsterdam, Amsterdam, The Netherlands., Klein SK; Department of Hematology, Meander Medisch Centrum, Amersfoort, The Netherlands.; Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Vellenga E; Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Huls GA; Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Muus P; Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Haematology, St. James University Hospital, Leeds, UK., Langemeijer SMC; Department of Laboratory Medicine - Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands., de Greef GE; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Te Boekhorst PAW; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Raaijmakers MHG; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., van Marwijk Kooy M; Department of Hematology, Isala Ziekenhuis, Zwolle, The Netherlands., Legdeur MC; Department of Hematology, Medisch Spectrum Twente, Enschede, The Netherlands., Wegman JJ; Department of Hematology, Deventer Ziekenhuis, Deventer, The Netherlands.; Department of Hematology, Amsterdam UMC, location AMC, Amsterdam, The Netherlands., Deenik W; Department of Internal Medicine, Tergooi Ziekenhuis, Hilversum, The Netherlands.; Department of Internal Medicine, Rijnstate, Arnhem, the Netherlands., de Weerdt O; Department of Internal Medicine, St. Antonius Ziekenhuis, Nieuwegein, The Netherlands., van Maanen-Lamme TM; Department of Internal Medicine, Dijklander Ziekenhuis, Hoorn, The Netherlands., Jobse P; Department of Internal Medicine, Admiraal de Ruyter Ziekenhuis, Goes, The Netherlands., van Kampen RJW; Department of Internal Medicine, Zuyderland Ziekenhuis, Geleen, The Netherlands., Beeker A; Department of Hematology, Spaarne Gasthuis, Hoofddorp, The Netherlands., Wijermans PW; Department of Hematology, Haaglanden Ziekenhuis, Den Haag, The Netherlands., Biemond BJ; Department of Hematology, Amsterdam UMC, location AMC, Amsterdam, The Netherlands., Tanis BC; Department of Internal Medicine, Groene Hart Ziekenhuis, Gouda, The Netherlands.; Department of General Practice Erasmus MC, Rotterdam, The Netherlands., van Esser JWJ; Department of Internal Medicine, Amphia Ziekenhuis, Breda, The Netherlands., Schaar CG; Department of Internal Medicine, Gelre Ziekenhuis, Apeldoorn, The Netherlands., Noordzij-Nooteboom HS; Department of Internal Medicine, Van Weel Bethesda Ziekenhuis, Dirksland, The Netherlands., Jacobs EMG; Department of Internal Medicine, Elkerliek Ziekenhuis, Helmond, The Netherlands., de Graaf AO; Department of Laboratory Medicine - Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands., Jongen-Lavrencic M; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Stevens-Kroef MJPL; Department of human genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Westers TM; Department of Hematology, Amsterdam UMC, location VUmc, Cancer Center Amsterdam, Amsterdam, The Netherlands., Jansen JH; Department of Laboratory Medicine - Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2024 Apr; Vol. 38 (4), pp. 840-850. Date of Electronic Publication: 2024 Jan 31.
DOI: 10.1038/s41375-024-02161-6
Abstrakt: A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: