background: many older patients with acute myeloid leukaemia die or cannot undergo allogeneic haematopoietic stem-cell transplantation (HSCT) due to toxicity caused by intensive chemotherapy. We hypothesised that replacing intensive chemotherapy with decitabine monotherapy could improve outcomes. methods: this open-label, randomised, controlled, phase 3 trial was conducted at 54 hospitals in nine European countries. patients aged 60 years and older who were newly diagnosed with acute myeloid leukaemia and had not yet been treated were enrolled if they had an eastern Cooperative Oncology Group performance status of 2 or less and were eligible for intensive chemotherapy. patients were randomly assigned (1:1) to receive decitabine or standard chemotherapy (known as 3 + 7). for the decitabine group, decitabine (20 mg/m2) was administered for the first 10 days in the first 28-day cycle, followed by 28-day cycles consisting of 5 days or 10 days of decitabine. For the 3 + 7 group, daunorubicin (60 mg/m2) was administered over the first 3 days and cytarabine (200 mg/m2) over the first 7 days, followed by 1-3 additional chemotherapy cycles. allogeneic HSCT was strongly encouraged. overall survival in the intention-to-treat population was the primary endpoint. safety was assessed in all patients who received the allocated treatment. This trial is registered at ClinicalTrials.gov, NCT02172872, and is closed to new participants. findings: between dec 1, 2014, and aug 20, 2019, 606 patients were randomly assigned to the decitabine (n=303) or 3 + 7 (n=303) group. following an interim analysis which showed futility, the IDMC recommended on may 22, 2019, that the study continued as planned considering the risks and benefits for the patients participating in the study. The cutoff date for the final analysis presented here was June 30, 2021. At a median follow-up of 4·0 years (IQR 2·9-4·8), 4-year overall survival was 26% (95% CI 21-32) in the decitabine group versus 30% (24-35) in the 3 + 7 group (hazard ratio for death 1·04 [95% CI 0·86-1·26]; p=0·68). rates of on-protocol allogeneic HSCT were similar between groups (122 [40%] of 303 patients for decitabine and 118 [39%] of 303 patients for 3+7). Rates of grade 3-5 adverse events were 254 (84%) of 302 patients in the decitabine group and 279 (94%) of 298 patients in the 3 + 7 group. The rates of grade 3-5 infections (41% [125 of 302] vs 53% [158 of 298]), oral mucositis (2% [seven of 302] vs 10% [31 of 298]) and diarrhoea (1% [three of 302] vs 8% [24 of 298]) were lower in the decitabine group than in the 3 + 7 group. Treatment-related deaths were reported for 12% (35 of 302) of patients in the decitabine group and 14% (41 of 298) in the 3 + 7 group. Interpretation: 10-day decitabine did not improve overall survival but showed a better safety profile compared with 3 + 7 chemotherapy in older patients with acute myeloid leukaemia eligible for intensive chemotherapy. Decitabine could be considered a better-tolerated and sufficiently efficacious alternative to 3 + 7 induction in fit older patients with acute myeloid leukaemia without favourable genetics. funding: Janssen pharmaceuticals.

Lübbert, M., Wijermans, P.w., Kicinski, M., Chantepie, S., Van der Velden, W., Noppeney, R., et al. (2023). 10-day decitabine versus 3 + 7 chemotherapy followed by allografting in older patients with acute myeloid leukaemia: an open-label, randomised, controlled, phase 3 trial. THE LANCET. HAEMATOLOGY, 10(11), 879-889 [10.1016/S2352-3026(23)00273-9].

10-day decitabine versus 3 + 7 chemotherapy followed by allografting in older patients with acute myeloid leukaemia: an open-label, randomised, controlled, phase 3 trial

Amadori, Sergio;Venditti, Adriano;
2023-11-01

Abstract

background: many older patients with acute myeloid leukaemia die or cannot undergo allogeneic haematopoietic stem-cell transplantation (HSCT) due to toxicity caused by intensive chemotherapy. We hypothesised that replacing intensive chemotherapy with decitabine monotherapy could improve outcomes. methods: this open-label, randomised, controlled, phase 3 trial was conducted at 54 hospitals in nine European countries. patients aged 60 years and older who were newly diagnosed with acute myeloid leukaemia and had not yet been treated were enrolled if they had an eastern Cooperative Oncology Group performance status of 2 or less and were eligible for intensive chemotherapy. patients were randomly assigned (1:1) to receive decitabine or standard chemotherapy (known as 3 + 7). for the decitabine group, decitabine (20 mg/m2) was administered for the first 10 days in the first 28-day cycle, followed by 28-day cycles consisting of 5 days or 10 days of decitabine. For the 3 + 7 group, daunorubicin (60 mg/m2) was administered over the first 3 days and cytarabine (200 mg/m2) over the first 7 days, followed by 1-3 additional chemotherapy cycles. allogeneic HSCT was strongly encouraged. overall survival in the intention-to-treat population was the primary endpoint. safety was assessed in all patients who received the allocated treatment. This trial is registered at ClinicalTrials.gov, NCT02172872, and is closed to new participants. findings: between dec 1, 2014, and aug 20, 2019, 606 patients were randomly assigned to the decitabine (n=303) or 3 + 7 (n=303) group. following an interim analysis which showed futility, the IDMC recommended on may 22, 2019, that the study continued as planned considering the risks and benefits for the patients participating in the study. The cutoff date for the final analysis presented here was June 30, 2021. At a median follow-up of 4·0 years (IQR 2·9-4·8), 4-year overall survival was 26% (95% CI 21-32) in the decitabine group versus 30% (24-35) in the 3 + 7 group (hazard ratio for death 1·04 [95% CI 0·86-1·26]; p=0·68). rates of on-protocol allogeneic HSCT were similar between groups (122 [40%] of 303 patients for decitabine and 118 [39%] of 303 patients for 3+7). Rates of grade 3-5 adverse events were 254 (84%) of 302 patients in the decitabine group and 279 (94%) of 298 patients in the 3 + 7 group. The rates of grade 3-5 infections (41% [125 of 302] vs 53% [158 of 298]), oral mucositis (2% [seven of 302] vs 10% [31 of 298]) and diarrhoea (1% [three of 302] vs 8% [24 of 298]) were lower in the decitabine group than in the 3 + 7 group. Treatment-related deaths were reported for 12% (35 of 302) of patients in the decitabine group and 14% (41 of 298) in the 3 + 7 group. Interpretation: 10-day decitabine did not improve overall survival but showed a better safety profile compared with 3 + 7 chemotherapy in older patients with acute myeloid leukaemia eligible for intensive chemotherapy. Decitabine could be considered a better-tolerated and sufficiently efficacious alternative to 3 + 7 induction in fit older patients with acute myeloid leukaemia without favourable genetics. funding: Janssen pharmaceuticals.
nov-2023
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/15
English
Con Impact Factor ISI
AML, decitabine, intensive chemotherapy, HSCT
Lübbert, M., Wijermans, P.w., Kicinski, M., Chantepie, S., Van der Velden, W., Noppeney, R., et al. (2023). 10-day decitabine versus 3 + 7 chemotherapy followed by allografting in older patients with acute myeloid leukaemia: an open-label, randomised, controlled, phase 3 trial. THE LANCET. HAEMATOLOGY, 10(11), 879-889 [10.1016/S2352-3026(23)00273-9].
Lübbert, M; Wijermans, Pw; Kicinski, M; Chantepie, S; Van der Velden, Wjfm; Noppeney, R; Griškevičius, L; Neubauer, A; Crysandt, M; Vrhovac, R; Lup...espandi
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
Lancet EORTC-GIMEMA AML021.pdf

solo utenti autorizzati

Descrizione: Articolo
Tipologia: Versione Editoriale (PDF)
Licenza: Copyright dell'editore
Dimensione 840.23 kB
Formato Adobe PDF
840.23 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/343123
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 4
social impact