TY - JOUR
T1 - Imetelstat achieves meaningful and durable transfusion independence in high transfusion–Burden patients with lower-risk myelodysplastic syndromes in a phase II study
AU - Steensma, David P.
AU - Fenaux, Pierre
AU - van Eygen, Koen
AU - Raza, Azra
AU - Santini, Valeria
AU - Germing, Ulrich
AU - Font, Patricia
AU - Diez-Campelo, Maria
AU - Thepot, Sylvain
AU - Vellenga, Edo
AU - Patnaik, Mrinal M.
AU - Jang, Jun Ho
AU - Varsos, Helen
AU - Bussolari, Jacqueline
AU - Rose, Esther
AU - Sherman, Laurie
AU - Sun, Libo
AU - Wan, Ying
AU - Dougherty, Souria
AU - Huang, Fei
AU - Feller, Faye
AU - Rizo, Aleksandra
AU - Platzbecker, Uwe
N1 - Funding Information:
The authors thank all the patients for their participation in this study and acknowledge the collaboration and commitment of all investigators and their staff. Editorial support for this publication was provided by Laurie Orloski, funded by Geron Corporation.
Publisher Copyright:
Copyright © 2020 American Society of Clinical Oncology. All rights reserved.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - PURPOSE Patients with lower-risk (LR) myelodysplastic syndromes (MDS) who are RBC transfusion dependent and have experienced relapse after or are refractory to erythropoiesis-stimulating agent (ESA) have limited treatment options. High telomerase activity and human telomerase reverse-transcription expression in clonal hematopoietic cells have been reported in patients with MDS. Imetelstat, a first-in-class competitive inhibitor of telomerase enzymatic activity, targets cells with active telomerase. We report efficacy, safety, and biomarker data for patients with LR MDS who are RBC transfusion dependent and who were relapsed/refractory to ESAs. PATIENTS AND METHODS In this two-part phase II/III study (MDS3001), the primary end point was 8-week RBC transfusion independence (TI) rate, with key secondary end points of 24-week RBC TI rate, TI duration, and hematologic improvement-erythroid. RESULTS Data from the phase II part of the study are reported. Of 57 patients enrolled and treated (overall population), 38 were non-del(5q) and hypomethylating agent and lenalidomide naïve (subset population). The 8- and 24-week RBC TI rates in the overall population were 37% and 23%, respectively, with a median TI duration of 65 weeks. In the subset population, 8- and 24-week RBC TI rates were 42% and 29%, respectively, with a median TI duration of 86 weeks. Eight-week TI rate was observed across all subgroups evaluated. Cytogenetic and mutational data revealed a reduction of the malignant clones, suggesting disease modification activity. The most common adverse events were cytopenias, typically reversible within 4 weeks. CONCLUSION Imetelstat treatment results in a meaningful, durable TI rate across a broad range of heavily transfused patients with LR MDS who are ineligible for or relapsed/refractory to ESAs. Biomarker analyses indicated effects on the mutant malignant clone.
AB - PURPOSE Patients with lower-risk (LR) myelodysplastic syndromes (MDS) who are RBC transfusion dependent and have experienced relapse after or are refractory to erythropoiesis-stimulating agent (ESA) have limited treatment options. High telomerase activity and human telomerase reverse-transcription expression in clonal hematopoietic cells have been reported in patients with MDS. Imetelstat, a first-in-class competitive inhibitor of telomerase enzymatic activity, targets cells with active telomerase. We report efficacy, safety, and biomarker data for patients with LR MDS who are RBC transfusion dependent and who were relapsed/refractory to ESAs. PATIENTS AND METHODS In this two-part phase II/III study (MDS3001), the primary end point was 8-week RBC transfusion independence (TI) rate, with key secondary end points of 24-week RBC TI rate, TI duration, and hematologic improvement-erythroid. RESULTS Data from the phase II part of the study are reported. Of 57 patients enrolled and treated (overall population), 38 were non-del(5q) and hypomethylating agent and lenalidomide naïve (subset population). The 8- and 24-week RBC TI rates in the overall population were 37% and 23%, respectively, with a median TI duration of 65 weeks. In the subset population, 8- and 24-week RBC TI rates were 42% and 29%, respectively, with a median TI duration of 86 weeks. Eight-week TI rate was observed across all subgroups evaluated. Cytogenetic and mutational data revealed a reduction of the malignant clones, suggesting disease modification activity. The most common adverse events were cytopenias, typically reversible within 4 weeks. CONCLUSION Imetelstat treatment results in a meaningful, durable TI rate across a broad range of heavily transfused patients with LR MDS who are ineligible for or relapsed/refractory to ESAs. Biomarker analyses indicated effects on the mutant malignant clone.
UR - http://www.scopus.com/inward/record.url?scp=85098331571&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85098331571&partnerID=8YFLogxK
U2 - 10.1200/JCO.20.01895
DO - 10.1200/JCO.20.01895
M3 - Article
C2 - 33108243
AN - SCOPUS:85098331571
SN - 0732-183X
VL - 39
SP - 48
EP - 56
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 1
ER -