Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine

Jacobien R Hilberink; Isabelle A van Zeventer; Dana A Chitu; Thomas Pabst; Saskia K Klein; Georg Stussi; Laimonas Griskevicius; Peter J M Valk; Jacqueline Cloos; Arjan A van de Loosdrecht; Dimitri Breems; Danielle van Lammeren-Venema; Rinske Boersma; Mojca Jongen-Lavrencic; Martin Fehr; Mels Hoogendoorn; Markus G Manz; Maaike Söhne; Rien van Marwijk Kooy; Dries Deeren; Marjolein W M van der Poel; Marie Cecile Legdeur; Lidwine Tick; Yves Chalandon; Emanuele Ammatuna; Sabine Blum; Bob Löwenberg; Gert J Ossenkoppele; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON); Swiss Group for Clinical Cancer Research (SAKK); Gerwin Huls

doi:10.1038/s41408-023-00850-6

Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine

Jacobien R Hilberink, Isabelle A van Zeventer, Dana A Chitu, Thomas Pabst, Saskia K Klein, Georg Stussi, Laimonas Griskevicius, Peter J M Valk, Jacqueline Cloos, Arjan A van de Loosdrecht, Dimitri Breems, Danielle van Lammeren-Venema, Rinske Boersma, Mojca Jongen-Lavrencic, Martin Fehr, Mels Hoogendoorn, Markus G Manz, Maaike Söhne, Rien van Marwijk Kooy, Dries DeerenMarjolein W M van der Poel, Marie Cecile Legdeur, Lidwine Tick, Yves Chalandon, Emanuele Ammatuna, Sabine Blum, Bob Löwenberg, Gert J Ossenkoppele, Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON), Swiss Group for Clinical Cancer Research (SAKK), Gerwin Huls^*

^*Corresponding author for this work

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

Abstract

Treatment choice according to the individual conditions remains challenging, particularly in older patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS). The impact of performance status, comorbidities, and physical functioning on survival is not well defined for patients treated with hypomethylating agents. Here we describe the impact of performance status (14% ECOG performance status 2), comorbidity (40% HCT-comorbidity index ≥ 2), and physical functioning (41% short physical performance battery < 9 and 17% ADL index < 6) on overall survival (OS) in 115 older patients (age ≥ 66 years) treated on a clinical trial with a 10-day decitabine schedule. None of the patient-related variables showed a significant association with OS. Multivariable analysis revealed that age > 76 years was significantly associated with reduced OS (HR 1.58; p = 0.043) and female sex was associated with superior OS (HR 0.62; p = 0.06). We further compared the genetic profiles of these subgroups. This revealed comparable mutational profiles in patients younger and older than 76 years, but, interestingly, revealed significantly more prevalent mutated ASXL1, STAG2, and U2AF1 in male compared to female patients. In this cohort of older patients treated with decitabine age and sex, but not comorbidities, physical functioning or cytogenetic risk were associated with overall survival.

Original language	English
Article number	93
Number of pages	9
Journal	Blood Cancer Journal
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41408-023-00850-6
Publication status	Published - 19 Jun 2023

Keywords

Humans
Male
Female
Aged
Decitabine/therapeutic use
Myelodysplastic Syndromes/genetics
Leukemia, Myeloid, Acute/genetics
Mutation
Treatment Outcome

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Cite this

Hilberink, J. R., van Zeventer, I. A., Chitu, D. A., Pabst, T., Klein, S. K., Stussi, G., Griskevicius, L., Valk, P. J. M., Cloos, J., van de Loosdrecht, A. A., Breems, D., van Lammeren-Venema, D., Boersma, R., Jongen-Lavrencic, M., Fehr, M., Hoogendoorn, M., Manz, M. G., Söhne, M., van Marwijk Kooy, R., ... Huls, G. (2023). Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine. Blood Cancer Journal, 13(1), Article 93. https://doi.org/10.1038/s41408-023-00850-6

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title = "Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine",

abstract = "Treatment choice according to the individual conditions remains challenging, particularly in older patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS). The impact of performance status, comorbidities, and physical functioning on survival is not well defined for patients treated with hypomethylating agents. Here we describe the impact of performance status (14% ECOG performance status 2), comorbidity (40% HCT-comorbidity index ≥ 2), and physical functioning (41% short physical performance battery < 9 and 17% ADL index < 6) on overall survival (OS) in 115 older patients (age ≥ 66 years) treated on a clinical trial with a 10-day decitabine schedule. None of the patient-related variables showed a significant association with OS. Multivariable analysis revealed that age > 76 years was significantly associated with reduced OS (HR 1.58; p = 0.043) and female sex was associated with superior OS (HR 0.62; p = 0.06). We further compared the genetic profiles of these subgroups. This revealed comparable mutational profiles in patients younger and older than 76 years, but, interestingly, revealed significantly more prevalent mutated ASXL1, STAG2, and U2AF1 in male compared to female patients. In this cohort of older patients treated with decitabine age and sex, but not comorbidities, physical functioning or cytogenetic risk were associated with overall survival.",

keywords = "Humans, Male, Female, Aged, Decitabine/therapeutic use, Myelodysplastic Syndromes/genetics, Leukemia, Myeloid, Acute/genetics, Mutation, Treatment Outcome",

author = "Hilberink, {Jacobien R} and {van Zeventer}, {Isabelle A} and Chitu, {Dana A} and Thomas Pabst and Klein, {Saskia K} and Georg Stussi and Laimonas Griskevicius and Valk, {Peter J M} and Jacqueline Cloos and {van de Loosdrecht}, {Arjan A} and Dimitri Breems and {van Lammeren-Venema}, Danielle and Rinske Boersma and Mojca Jongen-Lavrencic and Martin Fehr and Mels Hoogendoorn and Manz, {Markus G} and Maaike S{\"o}hne and {van Marwijk Kooy}, Rien and Dries Deeren and {van der Poel}, {Marjolein W M} and Legdeur, {Marie Cecile} and Lidwine Tick and Yves Chalandon and Emanuele Ammatuna and Sabine Blum and Bob L{\"o}wenberg and Ossenkoppele, {Gert J} and {Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON)} and {Swiss Group for Clinical Cancer Research (SAKK)} and Gerwin Huls",

note = "{\textcopyright} 2023. The Author(s).",

year = "2023",

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doi = "10.1038/s41408-023-00850-6",

language = "English",

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Hilberink, JR, van Zeventer, IA, Chitu, DA, Pabst, T, Klein, SK, Stussi, G, Griskevicius, L, Valk, PJM, Cloos, J, van de Loosdrecht, AA, Breems, D, van Lammeren-Venema, D, Boersma, R, Jongen-Lavrencic, M, Fehr, M, Hoogendoorn, M, Manz, MG, Söhne, M, van Marwijk Kooy, R, Deeren, D, van der Poel, MWM, Legdeur, MC, Tick, L, Chalandon, Y, Ammatuna, E, Blum, S, Löwenberg, B, Ossenkoppele, GJ, Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON), Swiss Group for Clinical Cancer Research (SAKK) & Huls, G 2023, 'Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine', Blood Cancer Journal, vol. 13, no. 1, 93. https://doi.org/10.1038/s41408-023-00850-6

TY - JOUR

T1 - Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine

AU - Hilberink, Jacobien R

AU - van Zeventer, Isabelle A

AU - Chitu, Dana A

AU - Pabst, Thomas

AU - Klein, Saskia K

AU - Stussi, Georg

AU - Griskevicius, Laimonas

AU - Valk, Peter J M

AU - Cloos, Jacqueline

AU - van de Loosdrecht, Arjan A

AU - Breems, Dimitri

AU - van Lammeren-Venema, Danielle

AU - Boersma, Rinske

AU - Jongen-Lavrencic, Mojca

AU - Fehr, Martin

AU - Hoogendoorn, Mels

AU - Manz, Markus G

AU - Söhne, Maaike

AU - van Marwijk Kooy, Rien

AU - Deeren, Dries

AU - van der Poel, Marjolein W M

AU - Legdeur, Marie Cecile

AU - Tick, Lidwine

AU - Chalandon, Yves

AU - Ammatuna, Emanuele

AU - Blum, Sabine

AU - Löwenberg, Bob

AU - Ossenkoppele, Gert J

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

AU - Swiss Group for Clinical Cancer Research (SAKK)

AU - Huls, Gerwin

PY - 2023/6/19

Y1 - 2023/6/19

N2 - Treatment choice according to the individual conditions remains challenging, particularly in older patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS). The impact of performance status, comorbidities, and physical functioning on survival is not well defined for patients treated with hypomethylating agents. Here we describe the impact of performance status (14% ECOG performance status 2), comorbidity (40% HCT-comorbidity index ≥ 2), and physical functioning (41% short physical performance battery < 9 and 17% ADL index < 6) on overall survival (OS) in 115 older patients (age ≥ 66 years) treated on a clinical trial with a 10-day decitabine schedule. None of the patient-related variables showed a significant association with OS. Multivariable analysis revealed that age > 76 years was significantly associated with reduced OS (HR 1.58; p = 0.043) and female sex was associated with superior OS (HR 0.62; p = 0.06). We further compared the genetic profiles of these subgroups. This revealed comparable mutational profiles in patients younger and older than 76 years, but, interestingly, revealed significantly more prevalent mutated ASXL1, STAG2, and U2AF1 in male compared to female patients. In this cohort of older patients treated with decitabine age and sex, but not comorbidities, physical functioning or cytogenetic risk were associated with overall survival.

AB - Treatment choice according to the individual conditions remains challenging, particularly in older patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS). The impact of performance status, comorbidities, and physical functioning on survival is not well defined for patients treated with hypomethylating agents. Here we describe the impact of performance status (14% ECOG performance status 2), comorbidity (40% HCT-comorbidity index ≥ 2), and physical functioning (41% short physical performance battery < 9 and 17% ADL index < 6) on overall survival (OS) in 115 older patients (age ≥ 66 years) treated on a clinical trial with a 10-day decitabine schedule. None of the patient-related variables showed a significant association with OS. Multivariable analysis revealed that age > 76 years was significantly associated with reduced OS (HR 1.58; p = 0.043) and female sex was associated with superior OS (HR 0.62; p = 0.06). We further compared the genetic profiles of these subgroups. This revealed comparable mutational profiles in patients younger and older than 76 years, but, interestingly, revealed significantly more prevalent mutated ASXL1, STAG2, and U2AF1 in male compared to female patients. In this cohort of older patients treated with decitabine age and sex, but not comorbidities, physical functioning or cytogenetic risk were associated with overall survival.

KW - Humans

KW - Male

KW - Female

KW - Aged

KW - Decitabine/therapeutic use

KW - Myelodysplastic Syndromes/genetics

KW - Leukemia, Myeloid, Acute/genetics

KW - Mutation

KW - Treatment Outcome

U2 - 10.1038/s41408-023-00850-6

DO - 10.1038/s41408-023-00850-6

M3 - Article

C2 - 37336890

SN - 2044-5385

VL - 13

JO - Blood Cancer Journal

JF - Blood Cancer Journal

IS - 1

M1 - 93

ER -