Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial

U. Platzbecker, V. Santini, P. Fenaux, MA. Sekeres, MR. Savona, YF. Madanat, M. Díez-Campelo, D. Valcárcel, T. Illmer, A. Jonášová, P. Bělohlávková, LJ. Sherman, T. Berry, S. Dougherty, S. Shah, Q. Xia, L. Sun, Y. Wan, F. Huang, A. Ikin, S....

. 2024 ; 403 (10423) : 249-260. [pub] 20231201

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu randomizované kontrolované studie, klinické zkoušky, fáze III, časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24007550
E-zdroje Online Plný text

NLK ProQuest Central od 1992-01-04 do Před 3 měsíci
Nursing & Allied Health Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Health & Medicine (ProQuest) od 1992-01-04 do Před 3 měsíci
Family Health Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Psychology Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Health Management Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Public Health Database (ProQuest) od 1992-01-04 do Před 3 měsíci

Odkazy

PubMed 38048786
DOI 10.1016/s0140-6736(23)01724-5
Knihovny.cz E-zdroje

BACKGROUND: Unmet medical needs remain in patients with red blood cell transfusion-dependent (RBC-TD) lower-risk myelodysplastic syndromes (LR-MDS) who are not responding to or are ineligible for erythropoiesis-stimulating agents (ESAs). Imetelstat, a competitive telomerase inhibitor, showed promising results in a phase 2 trial. We aimed to compare the RBC transfusion independence (RBC-TI) rate with imetelstat versus placebo in patients with RBC-TD LR-MDS. METHODS: In phase 3 of IMerge, a double-blind, placebo-controlled trial conducted in 118 sites including university hospitals, cancer centres, and outpatient clinics in 17 countries, patients (aged ≥18 years) with ESA-relapsed, ESA-refractory, or ESA-ineligible LR-MDS (low or intermediate-1 risk disease as per International Prognostic Scoring System [IPSS] criteria) were randomly assigned via a computer-generated schedule (2:1) to receive imetelstat 7·5 mg/kg or placebo, administered as a 2-h intravenous infusion, every 4 weeks until disease progression, unacceptable toxic effects, or withdrawal of consent. Randomisation was stratified by previous RBC transfusion burden and IPSS risk group. Patients, investigators, and those analysing the data were masked to group assignment. The primary endpoint was 8-week RBC-TI, defined as the proportion of patients without RBC transfusions for at least 8 consecutive weeks starting on the day of randomisation until subsequent anti-cancer therapy, if any. Primary efficacy analyses were performed in the intention-to-treat population, and safety analyses were conducted in patients who received at least one dose of trial medication or placebo. This trial is registered with ClinicalTrials.gov (NCT02598661; substudy active and recruiting). FINDINGS: Between Sept 11, 2019, and Oct 13, 2021, 178 patients were enrolled and randomly assigned (118 to imetelstat and 60 to placebo). 111 (62%) were male and 67 (38%) were female. 91 (77%) of 118 patients had discontinued treatment by data cutoff in the imetelstat group versus 45 (75%) in the placebo group; a further one patient in the placebo group did not receive treatment. Median follow-up was 19·5 months (IQR 12·0-23·4) in the imetelstat group and 17·5 months (12·1-22·7) in the placebo group. In the imetelstat group, 47 (40% [95% CI 30·9-49·3]) patients had an RBC-TI of at least 8 weeks versus nine (15% [7·1-26·6]) in the placebo group (rate difference 25% [9·9 to 36·9]; p=0·0008). Overall, 107 (91%) of 118 patients receiving imetelstat and 28 (47%) of 59 patients receiving placebo had grade 3-4 treatment-emergent adverse events. The most common treatment-emergent grade 3-4 adverse events in patients taking imetelstat were neutropenia (80 [68%] patients who received imetelstat vs two [3%] who received placebo) and thrombocytopenia (73 [62%] vs five [8%]). No treatment-related deaths were reported. INTERPRETATION: Imetelstat offers a novel mechanism of action with durable transfusion independence (approximately 1 year) and disease-modifying activity for heavily transfused patients with LR-MDS who are not responding to or are ineligible for ESAs. FUNDING: Janssen Research & Development before April 18, 2019, and Geron Corporation thereafter.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc24007550
003      
CZ-PrNML
005      
20240423160043.0
007      
ta
008      
240412s2024 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1016/S0140-6736(23)01724-5 $2 doi
035    __
$a (PubMed)38048786
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Platzbecker, Uwe $u Department of Hematology, Cellular Therapy, Infectious Diseases, and Hemostaseology, University Hospital Leipzig, Leipzig, Germany. Electronic address: uwe.platzbecker@medizin.uni-leipzig.de
245    10
$a Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial / $c U. Platzbecker, V. Santini, P. Fenaux, MA. Sekeres, MR. Savona, YF. Madanat, M. Díez-Campelo, D. Valcárcel, T. Illmer, A. Jonášová, P. Bělohlávková, LJ. Sherman, T. Berry, S. Dougherty, S. Shah, Q. Xia, L. Sun, Y. Wan, F. Huang, A. Ikin, S. Navada, F. Feller, RS. Komrokji, AM. Zeidan
520    9_
$a BACKGROUND: Unmet medical needs remain in patients with red blood cell transfusion-dependent (RBC-TD) lower-risk myelodysplastic syndromes (LR-MDS) who are not responding to or are ineligible for erythropoiesis-stimulating agents (ESAs). Imetelstat, a competitive telomerase inhibitor, showed promising results in a phase 2 trial. We aimed to compare the RBC transfusion independence (RBC-TI) rate with imetelstat versus placebo in patients with RBC-TD LR-MDS. METHODS: In phase 3 of IMerge, a double-blind, placebo-controlled trial conducted in 118 sites including university hospitals, cancer centres, and outpatient clinics in 17 countries, patients (aged ≥18 years) with ESA-relapsed, ESA-refractory, or ESA-ineligible LR-MDS (low or intermediate-1 risk disease as per International Prognostic Scoring System [IPSS] criteria) were randomly assigned via a computer-generated schedule (2:1) to receive imetelstat 7·5 mg/kg or placebo, administered as a 2-h intravenous infusion, every 4 weeks until disease progression, unacceptable toxic effects, or withdrawal of consent. Randomisation was stratified by previous RBC transfusion burden and IPSS risk group. Patients, investigators, and those analysing the data were masked to group assignment. The primary endpoint was 8-week RBC-TI, defined as the proportion of patients without RBC transfusions for at least 8 consecutive weeks starting on the day of randomisation until subsequent anti-cancer therapy, if any. Primary efficacy analyses were performed in the intention-to-treat population, and safety analyses were conducted in patients who received at least one dose of trial medication or placebo. This trial is registered with ClinicalTrials.gov (NCT02598661; substudy active and recruiting). FINDINGS: Between Sept 11, 2019, and Oct 13, 2021, 178 patients were enrolled and randomly assigned (118 to imetelstat and 60 to placebo). 111 (62%) were male and 67 (38%) were female. 91 (77%) of 118 patients had discontinued treatment by data cutoff in the imetelstat group versus 45 (75%) in the placebo group; a further one patient in the placebo group did not receive treatment. Median follow-up was 19·5 months (IQR 12·0-23·4) in the imetelstat group and 17·5 months (12·1-22·7) in the placebo group. In the imetelstat group, 47 (40% [95% CI 30·9-49·3]) patients had an RBC-TI of at least 8 weeks versus nine (15% [7·1-26·6]) in the placebo group (rate difference 25% [9·9 to 36·9]; p=0·0008). Overall, 107 (91%) of 118 patients receiving imetelstat and 28 (47%) of 59 patients receiving placebo had grade 3-4 treatment-emergent adverse events. The most common treatment-emergent grade 3-4 adverse events in patients taking imetelstat were neutropenia (80 [68%] patients who received imetelstat vs two [3%] who received placebo) and thrombocytopenia (73 [62%] vs five [8%]). No treatment-related deaths were reported. INTERPRETATION: Imetelstat offers a novel mechanism of action with durable transfusion independence (approximately 1 year) and disease-modifying activity for heavily transfused patients with LR-MDS who are not responding to or are ineligible for ESAs. FUNDING: Janssen Research & Development before April 18, 2019, and Geron Corporation thereafter.
650    _2
$a lidé $7 D006801
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a mladiství $7 D000293
650    _2
$a dospělí $7 D000328
650    _2
$a výsledek terapie $7 D016896
650    _2
$a erytropoéza $7 D004920
650    12
$a myelodysplastické syndromy $x farmakoterapie $7 D009190
650    12
$a trombocytopenie $x farmakoterapie $7 D013921
650    _2
$a dvojitá slepá metoda $7 D004311
650    _2
$a protokoly protinádorové kombinované chemoterapie $7 D000971
650    12
$a oligonukleotidy $7 D009841
655    _2
$a randomizované kontrolované studie $7 D016449
655    _2
$a klinické zkoušky, fáze III $7 D017428
655    _2
$a časopisecké články $7 D016428
700    1_
$a Santini, Valeria $u MDS Unit, AOU Careggi, University of Florence, Florence, Italy
700    1_
$a Fenaux, Pierre $u Hôpital Saint-Louis, Université de Paris 7, Paris, France
700    1_
$a Sekeres, Mikkael A $u Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA
700    1_
$a Savona, Michael R $u Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
700    1_
$a Madanat, Yazan F $u Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA
700    1_
$a Díez-Campelo, Maria $u Hematology Department, University Hospital of Salamanca, IBSAL, Salamanca, Spain
700    1_
$a Valcárcel, David $u Department of Hematology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
700    1_
$a Illmer, Thomas $u Hematology Private Practice, Dresden, Germany
700    1_
$a Jonášová, Anna $u 1st Medical Department-Hematology, Charles University General Hospital, Prague, Czech Republic
700    1_
$a Bělohlávková, Petra $u 4th Department of Internal Medicine-Haematology, Charles University Hospital, Hradec Kralove, Czech Republic
700    1_
$a Sherman, Laurie J $u Geron Corporation, Parsippany, NJ, USA
700    1_
$a Berry, Tymara $u Geron Corporation, Parsippany, NJ, USA
700    1_
$a Dougherty, Souria $u Geron Corporation, Parsippany, NJ, USA
700    1_
$a Shah, Sheetal $u Geron Corporation, Parsippany, NJ, USA
700    1_
$a Xia, Qi $u Geron Corporation, Parsippany, NJ, USA
700    1_
$a Sun, Libo $u Geron Corporation, Parsippany, NJ, USA
700    1_
$a Wan, Ying $u Geron Corporation, Parsippany, NJ, USA
700    1_
$a Huang, Fei $u Geron Corporation, Parsippany, NJ, USA
700    1_
$a Ikin, Annat $u Geron Corporation, Parsippany, NJ, USA
700    1_
$a Navada, Shyamala $u Geron Corporation, Parsippany, NJ, USA
700    1_
$a Feller, Faye $u Geron Corporation, Parsippany, NJ, USA
700    1_
$a Komrokji, Rami S $u Moffitt Cancer Center, Tampa, FL, USA
700    1_
$a Zeidan, Amer M $u Section of Hematology, Department of Internal Medicine, Yale School of Medicine and Yale Comprehensive Cancer Center, Yale University, New Haven, CT, USA
773    0_
$w MED00010161 $t Lancet $x 1474-547X $g Roč. 403, č. 10423 (2024), s. 249-260
856    41
$u https://pubmed.ncbi.nlm.nih.gov/38048786 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20240412 $b ABA008
991    __
$a 20240423160039 $b ABA008
999    __
$a ok $b bmc $g 2081508 $s 1217317
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2024 $b 403 $c 10423 $d 249-260 $e 20231201 $i 1474-547X $m Lancet $n Lancet $x MED00010161
LZP    __
$a Pubmed-20240412

Najít záznam

Citační ukazatele

Možnosti archivace