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
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 promisi...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Platzbecker, Uwe [verfasserIn] Santini, Valeria [verfasserIn] Fenaux, Pierre [verfasserIn] Sekeres, Mikkael A [verfasserIn] Savona, Michael R [verfasserIn] Madanat, Yazan F [verfasserIn] Díez-Campelo, Maria [verfasserIn] Valcárcel, David [verfasserIn] Illmer, Thomas [verfasserIn] Jonášová, Anna [verfasserIn] Bělohlávková, Petra [verfasserIn] Sherman, Laurie J [verfasserIn] Berry, Tymara [verfasserIn] Dougherty, Souria [verfasserIn] Shah, Sheetal [verfasserIn] Xia, Qi [verfasserIn] Sun, Libo [verfasserIn] Wan, Ying [verfasserIn] Huang, Fei [verfasserIn] Ikin, Annat [verfasserIn] Navada, Shyamala [verfasserIn] Feller, Faye [verfasserIn] Komrokji, Rami S [verfasserIn] Zeidan, Amer M [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2024 |
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| Übergeordnetes Werk: |
Enthalten in: No title available - 403, Seite 249-260 |
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| Übergeordnetes Werk: |
volume:403 ; pages:249-260 |
| DOI / URN: |
10.1016/S0140-6736(23)01724-5 |
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| Katalog-ID: |
ELV066659299 |
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| 100 | 1 | |a Platzbecker, Uwe |e verfasserin |4 aut | |
| 245 | 1 | 0 | |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 |
| 264 | 1 | |c 2024 | |
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| 337 | |a Computermedien |b c |2 rdamedia | ||
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| 520 | |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. | ||
| 700 | 1 | |a Santini, Valeria |e verfasserin |4 aut | |
| 700 | 1 | |a Fenaux, Pierre |e verfasserin |4 aut | |
| 700 | 1 | |a Sekeres, Mikkael A |e verfasserin |4 aut | |
| 700 | 1 | |a Savona, Michael R |e verfasserin |4 aut | |
| 700 | 1 | |a Madanat, Yazan F |e verfasserin |4 aut | |
| 700 | 1 | |a Díez-Campelo, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Valcárcel, David |e verfasserin |4 aut | |
| 700 | 1 | |a Illmer, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Jonášová, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Bělohlávková, Petra |e verfasserin |4 aut | |
| 700 | 1 | |a Sherman, Laurie J |e verfasserin |4 aut | |
| 700 | 1 | |a Berry, Tymara |e verfasserin |4 aut | |
| 700 | 1 | |a Dougherty, Souria |e verfasserin |4 aut | |
| 700 | 1 | |a Shah, Sheetal |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Libo |e verfasserin |4 aut | |
| 700 | 1 | |a Wan, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Ikin, Annat |e verfasserin |4 aut | |
| 700 | 1 | |a Navada, Shyamala |e verfasserin |4 aut | |
| 700 | 1 | |a Feller, Faye |e verfasserin |4 aut | |
| 700 | 1 | |a Komrokji, Rami S |e verfasserin |4 aut | |
| 700 | 1 | |a Zeidan, Amer M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t No title available |g 403, Seite 249-260 |w (DE-627)270128484 |x 0140-6736 |7 nnns |
| 773 | 1 | 8 | |g volume:403 |g pages:249-260 |
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2024 |
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10.1016/S0140-6736(23)01724-5 doi (DE-627)ELV066659299 (ELSEVIER)S0140-6736(23)01724-5 DE-627 ger DE-627 rda eng Platzbecker, Uwe verfasserin aut 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 2024 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Santini, Valeria verfasserin aut Fenaux, Pierre verfasserin aut Sekeres, Mikkael A verfasserin aut Savona, Michael R verfasserin aut Madanat, Yazan F verfasserin aut Díez-Campelo, Maria verfasserin aut Valcárcel, David verfasserin aut Illmer, Thomas verfasserin aut Jonášová, Anna verfasserin aut Bělohlávková, Petra verfasserin aut Sherman, Laurie J verfasserin aut Berry, Tymara verfasserin aut Dougherty, Souria verfasserin aut Shah, Sheetal verfasserin aut Xia, Qi verfasserin aut Sun, Libo verfasserin aut Wan, Ying verfasserin aut Huang, Fei verfasserin aut Ikin, Annat verfasserin aut Navada, Shyamala verfasserin aut Feller, Faye verfasserin aut Komrokji, Rami S verfasserin aut Zeidan, Amer M verfasserin aut Enthalten in No title available 403, Seite 249-260 (DE-627)270128484 0140-6736 nnns volume:403 pages:249-260 GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_213 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 403 249-260 |
| spelling |
10.1016/S0140-6736(23)01724-5 doi (DE-627)ELV066659299 (ELSEVIER)S0140-6736(23)01724-5 DE-627 ger DE-627 rda eng Platzbecker, Uwe verfasserin aut 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 2024 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Santini, Valeria verfasserin aut Fenaux, Pierre verfasserin aut Sekeres, Mikkael A verfasserin aut Savona, Michael R verfasserin aut Madanat, Yazan F verfasserin aut Díez-Campelo, Maria verfasserin aut Valcárcel, David verfasserin aut Illmer, Thomas verfasserin aut Jonášová, Anna verfasserin aut Bělohlávková, Petra verfasserin aut Sherman, Laurie J verfasserin aut Berry, Tymara verfasserin aut Dougherty, Souria verfasserin aut Shah, Sheetal verfasserin aut Xia, Qi verfasserin aut Sun, Libo verfasserin aut Wan, Ying verfasserin aut Huang, Fei verfasserin aut Ikin, Annat verfasserin aut Navada, Shyamala verfasserin aut Feller, Faye verfasserin aut Komrokji, Rami S verfasserin aut Zeidan, Amer M verfasserin aut Enthalten in No title available 403, Seite 249-260 (DE-627)270128484 0140-6736 nnns volume:403 pages:249-260 GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_213 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 403 249-260 |
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10.1016/S0140-6736(23)01724-5 doi (DE-627)ELV066659299 (ELSEVIER)S0140-6736(23)01724-5 DE-627 ger DE-627 rda eng Platzbecker, Uwe verfasserin aut 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 2024 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Santini, Valeria verfasserin aut Fenaux, Pierre verfasserin aut Sekeres, Mikkael A verfasserin aut Savona, Michael R verfasserin aut Madanat, Yazan F verfasserin aut Díez-Campelo, Maria verfasserin aut Valcárcel, David verfasserin aut Illmer, Thomas verfasserin aut Jonášová, Anna verfasserin aut Bělohlávková, Petra verfasserin aut Sherman, Laurie J verfasserin aut Berry, Tymara verfasserin aut Dougherty, Souria verfasserin aut Shah, Sheetal verfasserin aut Xia, Qi verfasserin aut Sun, Libo verfasserin aut Wan, Ying verfasserin aut Huang, Fei verfasserin aut Ikin, Annat verfasserin aut Navada, Shyamala verfasserin aut Feller, Faye verfasserin aut Komrokji, Rami S verfasserin aut Zeidan, Amer M verfasserin aut Enthalten in No title available 403, Seite 249-260 (DE-627)270128484 0140-6736 nnns volume:403 pages:249-260 GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_213 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 403 249-260 |
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10.1016/S0140-6736(23)01724-5 doi (DE-627)ELV066659299 (ELSEVIER)S0140-6736(23)01724-5 DE-627 ger DE-627 rda eng Platzbecker, Uwe verfasserin aut 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 2024 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Santini, Valeria verfasserin aut Fenaux, Pierre verfasserin aut Sekeres, Mikkael A verfasserin aut Savona, Michael R verfasserin aut Madanat, Yazan F verfasserin aut Díez-Campelo, Maria verfasserin aut Valcárcel, David verfasserin aut Illmer, Thomas verfasserin aut Jonášová, Anna verfasserin aut Bělohlávková, Petra verfasserin aut Sherman, Laurie J verfasserin aut Berry, Tymara verfasserin aut Dougherty, Souria verfasserin aut Shah, Sheetal verfasserin aut Xia, Qi verfasserin aut Sun, Libo verfasserin aut Wan, Ying verfasserin aut Huang, Fei verfasserin aut Ikin, Annat verfasserin aut Navada, Shyamala verfasserin aut Feller, Faye verfasserin aut Komrokji, Rami S verfasserin aut Zeidan, Amer M verfasserin aut Enthalten in No title available 403, Seite 249-260 (DE-627)270128484 0140-6736 nnns volume:403 pages:249-260 GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_213 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 403 249-260 |
| allfieldsSound |
10.1016/S0140-6736(23)01724-5 doi (DE-627)ELV066659299 (ELSEVIER)S0140-6736(23)01724-5 DE-627 ger DE-627 rda eng Platzbecker, Uwe verfasserin aut 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 2024 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Santini, Valeria verfasserin aut Fenaux, Pierre verfasserin aut Sekeres, Mikkael A verfasserin aut Savona, Michael R verfasserin aut Madanat, Yazan F verfasserin aut Díez-Campelo, Maria verfasserin aut Valcárcel, David verfasserin aut Illmer, Thomas verfasserin aut Jonášová, Anna verfasserin aut Bělohlávková, Petra verfasserin aut Sherman, Laurie J verfasserin aut Berry, Tymara verfasserin aut Dougherty, Souria verfasserin aut Shah, Sheetal verfasserin aut Xia, Qi verfasserin aut Sun, Libo verfasserin aut Wan, Ying verfasserin aut Huang, Fei verfasserin aut Ikin, Annat verfasserin aut Navada, Shyamala verfasserin aut Feller, Faye verfasserin aut Komrokji, Rami S verfasserin aut Zeidan, Amer M verfasserin aut Enthalten in No title available 403, Seite 249-260 (DE-627)270128484 0140-6736 nnns volume:403 pages:249-260 GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_213 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 403 249-260 |
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Platzbecker, Uwe @@aut@@ Santini, Valeria @@aut@@ Fenaux, Pierre @@aut@@ Sekeres, Mikkael A @@aut@@ Savona, Michael R @@aut@@ Madanat, Yazan F @@aut@@ Díez-Campelo, Maria @@aut@@ Valcárcel, David @@aut@@ Illmer, Thomas @@aut@@ Jonášová, Anna @@aut@@ Bělohlávková, Petra @@aut@@ Sherman, Laurie J @@aut@@ Berry, Tymara @@aut@@ Dougherty, Souria @@aut@@ Shah, Sheetal @@aut@@ Xia, Qi @@aut@@ Sun, Libo @@aut@@ Wan, Ying @@aut@@ Huang, Fei @@aut@@ Ikin, Annat @@aut@@ Navada, Shyamala @@aut@@ Feller, Faye @@aut@@ Komrokji, Rami S @@aut@@ Zeidan, Amer M @@aut@@ |
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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%]). 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Platzbecker, Uwe |
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Platzbecker, Uwe 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 |
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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 |
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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 |
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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 |
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Platzbecker, Uwe Santini, Valeria Fenaux, Pierre Sekeres, Mikkael A Savona, Michael R Madanat, Yazan F Díez-Campelo, Maria Valcárcel, David Illmer, Thomas Jonášová, Anna Bělohlávková, Petra Sherman, Laurie J Berry, Tymara Dougherty, Souria Shah, Sheetal Xia, Qi Sun, Libo Wan, Ying Huang, Fei Ikin, Annat Navada, Shyamala Feller, Faye Komrokji, Rami S Zeidan, Amer M |
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Elektronische Aufsätze |
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10.1016/S0140-6736(23)01724-5 |
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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 |
| title_auth |
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 |
| abstract |
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. |
| abstractGer |
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. |
| abstract_unstemmed |
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. |
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| title_short |
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 |
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Santini, Valeria Fenaux, Pierre Sekeres, Mikkael A Savona, Michael R Madanat, Yazan F Díez-Campelo, Maria Valcárcel, David Illmer, Thomas Jonášová, Anna Bělohlávková, Petra Sherman, Laurie J Berry, Tymara Dougherty, Souria Shah, Sheetal Xia, Qi Sun, Libo Wan, Ying Huang, Fei Ikin, Annat Navada, Shyamala Feller, Faye Komrokji, Rami S Zeidan, Amer M |
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Santini, Valeria Fenaux, Pierre Sekeres, Mikkael A Savona, Michael R Madanat, Yazan F Díez-Campelo, Maria Valcárcel, David Illmer, Thomas Jonášová, Anna Bělohlávková, Petra Sherman, Laurie J Berry, Tymara Dougherty, Souria Shah, Sheetal Xia, Qi Sun, Libo Wan, Ying Huang, Fei Ikin, Annat Navada, Shyamala Feller, Faye Komrokji, Rami S Zeidan, Amer M |
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| doi_str |
10.1016/S0140-6736(23)01724-5 |
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2024-07-06T18:32:06.471Z |
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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%]). 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