A randomized phase III study of standard versus high-dose cytarabine with or without vorinostat for AML

Guillermo Garcia-Manero; Nikolai A. Podoltsev; Megan Othus; John M. Pagel; Jerald P. Radich; Min Fang; David A. Rizzieri; Guido Marcucci; Stephen A. Strickland; Mark R. Litzow; M. Lynn Savoie; Bruno C. Medeiros; Mikkael A. Sekeres; Tara L. Lin; Geoffrey L. Uy; Bayard L. Powell; Jonathan E. Kolitz; Richard A. Larson; Richard M. Stone; David Claxton; James Essell; Selina M. Luger; Sanjay R. Mohan; Anna Moseley; Frederick R. Appelbaum; Harry P. Erba

doi:10.1038/s41375-023-02073-x

A randomized phase III study of standard versus high-dose cytarabine with or without vorinostat for AML

Guillermo Garcia-Manero, Nikolai A. Podoltsev, Megan Othus, John M. Pagel, Jerald P. Radich, Min Fang, David A. Rizzieri, Guido Marcucci, Stephen A. Strickland, Mark R. Litzow, M. Lynn Savoie, Bruno C. Medeiros, Mikkael A. Sekeres, Tara L. Lin, Geoffrey L. Uy, Bayard L. Powell, Jonathan E. Kolitz, Richard A. Larson, Richard M. Stone, David ClaxtonJames Essell, Selina M. Luger, Sanjay R. Mohan, Anna Moseley, Frederick R. Appelbaum, Harry P. Erba

Hematology

Research output: Contribution to journal › Article › peer-review

Abstract

Prior experience indicated that use of higher doses of cytarabine during induction for acute myeloid leukemia (AML) with a histone deacetylase inhibitor resulted in high response rates. S1203 was a randomized multicenter trial for previously untreated patients aged 18–60 with AML which compared daunorubicin and cytarabine (DA), idarubicin with higher dose cytarabine (IA) and IA with vorinostat (IA + V). The primary endpoint was event free survival (EFS). 738 patients were randomized: 261 to each DA and IA arms and 216 to the IA + V arm. 96, 456, and 150 patients had favorable-, intermediate-, and unfavorable-risk cytogenetics, respectively. 152 were NPM1 and 158 FLT3 mutated. The overall remission rate was 77.5% including 62.5% CR and 15.0% CRi. No differences in remission, EFS, or overall survival were observed among the 3 arms except for the favorable cytogenetics subset who had improved outcomes with DA and postremission high dose cytarabine. A trend towards increased toxicity was observed with the IA and IA + V arms. The use of higher dose cytarabine during induction therapy in younger patients with AML, with or without vorinostat, does not result in improved outcomes. (Funded by the US National Institutes of Health and others, ClinicalTrials.gov number, NCT01802333.)

Original language	English (US)
Journal	Leukemia
DOIs	https://doi.org/10.1038/s41375-023-02073-x
State	Accepted/In press - 2023

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

Access to Document

10.1038/s41375-023-02073-x

Cite this

Garcia-Manero, G., Podoltsev, N. A., Othus, M., Pagel, J. M., Radich, J. P., Fang, M., Rizzieri, D. A., Marcucci, G., Strickland, S. A., Litzow, M. R., Savoie, M. L., Medeiros, B. C., Sekeres, M. A., Lin, T. L., Uy, G. L., Powell, B. L., Kolitz, J. E., Larson, R. A., Stone, R. M., ... Erba, H. P. (Accepted/In press). A randomized phase III study of standard versus high-dose cytarabine with or without vorinostat for AML. Leukemia. https://doi.org/10.1038/s41375-023-02073-x

Garcia-Manero, G, Podoltsev, NA, Othus, M, Pagel, JM, Radich, JP, Fang, M, Rizzieri, DA, Marcucci, G, Strickland, SA, Litzow, MR, Savoie, ML, Medeiros, BC, Sekeres, MA, Lin, TL, Uy, GL, Powell, BL, Kolitz, JE, Larson, RA, Stone, RM, Claxton, D, Essell, J, Luger, SM, Mohan, SR, Moseley, A, Appelbaum, FR & Erba, HP 2023, 'A randomized phase III study of standard versus high-dose cytarabine with or without vorinostat for AML', Leukemia. https://doi.org/10.1038/s41375-023-02073-x

@article{3094a2049b884b89842e4a05cf16553e,

title = "A randomized phase III study of standard versus high-dose cytarabine with or without vorinostat for AML",

abstract = "Prior experience indicated that use of higher doses of cytarabine during induction for acute myeloid leukemia (AML) with a histone deacetylase inhibitor resulted in high response rates. S1203 was a randomized multicenter trial for previously untreated patients aged 18–60 with AML which compared daunorubicin and cytarabine (DA), idarubicin with higher dose cytarabine (IA) and IA with vorinostat (IA + V). The primary endpoint was event free survival (EFS). 738 patients were randomized: 261 to each DA and IA arms and 216 to the IA + V arm. 96, 456, and 150 patients had favorable-, intermediate-, and unfavorable-risk cytogenetics, respectively. 152 were NPM1 and 158 FLT3 mutated. The overall remission rate was 77.5% including 62.5% CR and 15.0% CRi. No differences in remission, EFS, or overall survival were observed among the 3 arms except for the favorable cytogenetics subset who had improved outcomes with DA and postremission high dose cytarabine. A trend towards increased toxicity was observed with the IA and IA + V arms. The use of higher dose cytarabine during induction therapy in younger patients with AML, with or without vorinostat, does not result in improved outcomes. (Funded by the US National Institutes of Health and others, ClinicalTrials.gov number, NCT01802333.)",

author = "Guillermo Garcia-Manero and Podoltsev, {Nikolai A.} and Megan Othus and Pagel, {John M.} and Radich, {Jerald P.} and Min Fang and Rizzieri, {David A.} and Guido Marcucci and Strickland, {Stephen A.} and Litzow, {Mark R.} and Savoie, {M. Lynn} and Medeiros, {Bruno C.} and Sekeres, {Mikkael A.} and Lin, {Tara L.} and Uy, {Geoffrey L.} and Powell, {Bayard L.} and Kolitz, {Jonathan E.} and Larson, {Richard A.} and Stone, {Richard M.} and David Claxton and James Essell and Luger, {Selina M.} and Mohan, {Sanjay R.} and Anna Moseley and Appelbaum, {Frederick R.} and Erba, {Harry P.}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2023",

doi = "10.1038/s41375-023-02073-x",

language = "English (US)",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - A randomized phase III study of standard versus high-dose cytarabine with or without vorinostat for AML

AU - Garcia-Manero, Guillermo

AU - Podoltsev, Nikolai A.

AU - Othus, Megan

AU - Pagel, John M.

AU - Radich, Jerald P.

AU - Fang, Min

AU - Rizzieri, David A.

AU - Marcucci, Guido

AU - Strickland, Stephen A.

AU - Litzow, Mark R.

AU - Savoie, M. Lynn

AU - Medeiros, Bruno C.

AU - Sekeres, Mikkael A.

AU - Lin, Tara L.

AU - Uy, Geoffrey L.

AU - Powell, Bayard L.

AU - Kolitz, Jonathan E.

AU - Larson, Richard A.

AU - Stone, Richard M.

AU - Claxton, David

AU - Essell, James

AU - Luger, Selina M.

AU - Mohan, Sanjay R.

AU - Moseley, Anna

AU - Appelbaum, Frederick R.

AU - Erba, Harry P.

PY - 2023

Y1 - 2023

N2 - Prior experience indicated that use of higher doses of cytarabine during induction for acute myeloid leukemia (AML) with a histone deacetylase inhibitor resulted in high response rates. S1203 was a randomized multicenter trial for previously untreated patients aged 18–60 with AML which compared daunorubicin and cytarabine (DA), idarubicin with higher dose cytarabine (IA) and IA with vorinostat (IA + V). The primary endpoint was event free survival (EFS). 738 patients were randomized: 261 to each DA and IA arms and 216 to the IA + V arm. 96, 456, and 150 patients had favorable-, intermediate-, and unfavorable-risk cytogenetics, respectively. 152 were NPM1 and 158 FLT3 mutated. The overall remission rate was 77.5% including 62.5% CR and 15.0% CRi. No differences in remission, EFS, or overall survival were observed among the 3 arms except for the favorable cytogenetics subset who had improved outcomes with DA and postremission high dose cytarabine. A trend towards increased toxicity was observed with the IA and IA + V arms. The use of higher dose cytarabine during induction therapy in younger patients with AML, with or without vorinostat, does not result in improved outcomes. (Funded by the US National Institutes of Health and others, ClinicalTrials.gov number, NCT01802333.)

AB - Prior experience indicated that use of higher doses of cytarabine during induction for acute myeloid leukemia (AML) with a histone deacetylase inhibitor resulted in high response rates. S1203 was a randomized multicenter trial for previously untreated patients aged 18–60 with AML which compared daunorubicin and cytarabine (DA), idarubicin with higher dose cytarabine (IA) and IA with vorinostat (IA + V). The primary endpoint was event free survival (EFS). 738 patients were randomized: 261 to each DA and IA arms and 216 to the IA + V arm. 96, 456, and 150 patients had favorable-, intermediate-, and unfavorable-risk cytogenetics, respectively. 152 were NPM1 and 158 FLT3 mutated. The overall remission rate was 77.5% including 62.5% CR and 15.0% CRi. No differences in remission, EFS, or overall survival were observed among the 3 arms except for the favorable cytogenetics subset who had improved outcomes with DA and postremission high dose cytarabine. A trend towards increased toxicity was observed with the IA and IA + V arms. The use of higher dose cytarabine during induction therapy in younger patients with AML, with or without vorinostat, does not result in improved outcomes. (Funded by the US National Institutes of Health and others, ClinicalTrials.gov number, NCT01802333.)

UR - http://www.scopus.com/inward/record.url?scp=85175974444&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85175974444&partnerID=8YFLogxK

U2 - 10.1038/s41375-023-02073-x

DO - 10.1038/s41375-023-02073-x

M3 - Article

C2 - 37935977

AN - SCOPUS:85175974444

SN - 0887-6924

JO - Leukemia

JF - Leukemia

ER -

A randomized phase III study of standard versus high-dose cytarabine with or without vorinostat for AML

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this