Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients

Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON)

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The prevention of relapse is the major therapeutic challenge in older patients with acute myeloid leukemia (AML) who have obtained a complete remission (CR) on intensive chemotherapy. In this randomized phase 3 study (HOVON97) in older patients (≥60 years) with AML or myelodysplastic syndrome with refractory anemia with excess of blasts, in CR/CR with incomplete hematologic recovery (CRi) after at least 2 cycles of intensive chemotherapy, we assessed the value of azacitidine as postremission therapy with respect to disease-free survival (DFS; primary end point) and overall survival (OS; secondary end point). In total, 116 eligible patients were randomly (1:1) assigned to either observation (N = 60) or azacitidine maintenance (N = 56; 50 mg/m2, subcutaneously, days 1-5, every 4 weeks) until relapse, for a maximum of 12 cycles. Fifty-five patients received at least 1 cycle of azacitidine, 46 at least 4 cycles, and 35 at least 12 cycles. The maintenance treatment with azacitidine was feasible. DFS was significantly better for the azacitidine treatment group (logrank; P = .04), as well as after adjustment for poor-risk cytogenetic abnormalities at diagnosis and platelet count at randomization (as surrogate for CR vs CRi; Cox regression; hazard ratio, 0.62; 95% confidence interval, 0.41-0.95; P = .026). The 12-month DFS was estimated at 64% for the azacitidine group and 42% for the control group. OS did not differ between treatment groups, with and without censoring for allogeneic hematopoietic cell transplantation. Rescue treatment was used more often in the observation group (n = 32) than in the azacitidine maintenance group (n = 9). We conclude that azacitidine maintenance after CR/CRi after intensive chemotherapy is feasible and significantly improves DFS. The study is registered with The Netherlands Trial Registry (NTR1810) and EudraCT (2008-001290-15).
Original languageEnglish
Pages (from-to)1457-1464
JournalBlood
Volume133
Issue number13
DOIs
Publication statusPublished - 2019

Cite this

Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). / Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients. In: Blood. 2019 ; Vol. 133, No. 13. pp. 1457-1464.
@article{c7217adb122d44559221f037a4c09fe7,
title = "Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients",
abstract = "The prevention of relapse is the major therapeutic challenge in older patients with acute myeloid leukemia (AML) who have obtained a complete remission (CR) on intensive chemotherapy. In this randomized phase 3 study (HOVON97) in older patients (≥60 years) with AML or myelodysplastic syndrome with refractory anemia with excess of blasts, in CR/CR with incomplete hematologic recovery (CRi) after at least 2 cycles of intensive chemotherapy, we assessed the value of azacitidine as postremission therapy with respect to disease-free survival (DFS; primary end point) and overall survival (OS; secondary end point). In total, 116 eligible patients were randomly (1:1) assigned to either observation (N = 60) or azacitidine maintenance (N = 56; 50 mg/m2, subcutaneously, days 1-5, every 4 weeks) until relapse, for a maximum of 12 cycles. Fifty-five patients received at least 1 cycle of azacitidine, 46 at least 4 cycles, and 35 at least 12 cycles. The maintenance treatment with azacitidine was feasible. DFS was significantly better for the azacitidine treatment group (logrank; P = .04), as well as after adjustment for poor-risk cytogenetic abnormalities at diagnosis and platelet count at randomization (as surrogate for CR vs CRi; Cox regression; hazard ratio, 0.62; 95{\%} confidence interval, 0.41-0.95; P = .026). The 12-month DFS was estimated at 64{\%} for the azacitidine group and 42{\%} for the control group. OS did not differ between treatment groups, with and without censoring for allogeneic hematopoietic cell transplantation. Rescue treatment was used more often in the observation group (n = 32) than in the azacitidine maintenance group (n = 9). We conclude that azacitidine maintenance after CR/CRi after intensive chemotherapy is feasible and significantly improves DFS. The study is registered with The Netherlands Trial Registry (NTR1810) and EudraCT (2008-001290-15).",
author = "{Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON)} and Gerwin Huls and Chitu, {Dana A.} and Violaine Havelange and Mojca Jongen-Lavrencic and {van de Loosdrecht}, {Arjan A.} and Biemond, {Bart J.} and Harm Sinnige and Beata Hodossy and Carlos Graux and Kooy, {Rien van Marwijk} and {de Weerdt}, Okke and Dimitri Breems and Saskia Klein and Kuball, {J. rgen} and Dries Deeren and Wim Terpstra and Marie-Christiane Vekemans and Ossenkoppele, {Gert J.} and Edo Vellenga and Bob L{\"o}wenberg",
year = "2019",
doi = "10.1182/blood-2018-10-879866",
language = "English",
volume = "133",
pages = "1457--1464",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "13",

}

Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) 2019, 'Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients' Blood, vol. 133, no. 13, pp. 1457-1464. https://doi.org/10.1182/blood-2018-10-879866

Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients. / Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON).

In: Blood, Vol. 133, No. 13, 2019, p. 1457-1464.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients

AU - Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON)

AU - Huls, Gerwin

AU - Chitu, Dana A.

AU - Havelange, Violaine

AU - Jongen-Lavrencic, Mojca

AU - van de Loosdrecht, Arjan A.

AU - Biemond, Bart J.

AU - Sinnige, Harm

AU - Hodossy, Beata

AU - Graux, Carlos

AU - Kooy, Rien van Marwijk

AU - de Weerdt, Okke

AU - Breems, Dimitri

AU - Klein, Saskia

AU - Kuball, J. rgen

AU - Deeren, Dries

AU - Terpstra, Wim

AU - Vekemans, Marie-Christiane

AU - Ossenkoppele, Gert J.

AU - Vellenga, Edo

AU - Löwenberg, Bob

PY - 2019

Y1 - 2019

N2 - The prevention of relapse is the major therapeutic challenge in older patients with acute myeloid leukemia (AML) who have obtained a complete remission (CR) on intensive chemotherapy. In this randomized phase 3 study (HOVON97) in older patients (≥60 years) with AML or myelodysplastic syndrome with refractory anemia with excess of blasts, in CR/CR with incomplete hematologic recovery (CRi) after at least 2 cycles of intensive chemotherapy, we assessed the value of azacitidine as postremission therapy with respect to disease-free survival (DFS; primary end point) and overall survival (OS; secondary end point). In total, 116 eligible patients were randomly (1:1) assigned to either observation (N = 60) or azacitidine maintenance (N = 56; 50 mg/m2, subcutaneously, days 1-5, every 4 weeks) until relapse, for a maximum of 12 cycles. Fifty-five patients received at least 1 cycle of azacitidine, 46 at least 4 cycles, and 35 at least 12 cycles. The maintenance treatment with azacitidine was feasible. DFS was significantly better for the azacitidine treatment group (logrank; P = .04), as well as after adjustment for poor-risk cytogenetic abnormalities at diagnosis and platelet count at randomization (as surrogate for CR vs CRi; Cox regression; hazard ratio, 0.62; 95% confidence interval, 0.41-0.95; P = .026). The 12-month DFS was estimated at 64% for the azacitidine group and 42% for the control group. OS did not differ between treatment groups, with and without censoring for allogeneic hematopoietic cell transplantation. Rescue treatment was used more often in the observation group (n = 32) than in the azacitidine maintenance group (n = 9). We conclude that azacitidine maintenance after CR/CRi after intensive chemotherapy is feasible and significantly improves DFS. The study is registered with The Netherlands Trial Registry (NTR1810) and EudraCT (2008-001290-15).

AB - The prevention of relapse is the major therapeutic challenge in older patients with acute myeloid leukemia (AML) who have obtained a complete remission (CR) on intensive chemotherapy. In this randomized phase 3 study (HOVON97) in older patients (≥60 years) with AML or myelodysplastic syndrome with refractory anemia with excess of blasts, in CR/CR with incomplete hematologic recovery (CRi) after at least 2 cycles of intensive chemotherapy, we assessed the value of azacitidine as postremission therapy with respect to disease-free survival (DFS; primary end point) and overall survival (OS; secondary end point). In total, 116 eligible patients were randomly (1:1) assigned to either observation (N = 60) or azacitidine maintenance (N = 56; 50 mg/m2, subcutaneously, days 1-5, every 4 weeks) until relapse, for a maximum of 12 cycles. Fifty-five patients received at least 1 cycle of azacitidine, 46 at least 4 cycles, and 35 at least 12 cycles. The maintenance treatment with azacitidine was feasible. DFS was significantly better for the azacitidine treatment group (logrank; P = .04), as well as after adjustment for poor-risk cytogenetic abnormalities at diagnosis and platelet count at randomization (as surrogate for CR vs CRi; Cox regression; hazard ratio, 0.62; 95% confidence interval, 0.41-0.95; P = .026). The 12-month DFS was estimated at 64% for the azacitidine group and 42% for the control group. OS did not differ between treatment groups, with and without censoring for allogeneic hematopoietic cell transplantation. Rescue treatment was used more often in the observation group (n = 32) than in the azacitidine maintenance group (n = 9). We conclude that azacitidine maintenance after CR/CRi after intensive chemotherapy is feasible and significantly improves DFS. The study is registered with The Netherlands Trial Registry (NTR1810) and EudraCT (2008-001290-15).

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85064118597&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30630862

U2 - 10.1182/blood-2018-10-879866

DO - 10.1182/blood-2018-10-879866

M3 - Article

VL - 133

SP - 1457

EP - 1464

JO - Blood

JF - Blood

SN - 0006-4971

IS - 13

ER -