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

Blood Cancer J. 2023 Jun 19;13(1):93. doi: 10.1038/s41408-023-00850-6.

Authors

Jacobien R Hilberink¹, Isabelle A van Zeventer¹, Dana A Chitu², Thomas Pabst³, Saskia K Klein^{1

4}, Georg Stussi⁵, Laimonas Griskevicius⁶, Peter J M Valk⁷, Jacqueline Cloos⁸, Arjan A van de Loosdrecht⁸, Dimitri Breems⁹, Danielle van Lammeren-Venema¹⁰, Rinske Boersma¹¹, Mojca Jongen-Lavrencic⁷, Martin Fehr¹², Mels Hoogendoorn¹³, Markus G Manz¹⁴, Maaike Söhne¹⁵, Rien van Marwijk Kooy¹⁶, Dries Deeren¹⁷, Marjolein W M van der Poel¹⁸, Marie Cecile Legdeur¹⁹, Lidwine Tick²⁰, Yves Chalandon²¹, Emanuele Ammatuna¹, Sabine Blum²², Bob Löwenberg⁷, Gert J Ossenkoppele⁸; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON); Swiss Group for Clinical Cancer Research (SAKK); Gerwin Huls²³

Affiliations

¹ Department of Hematology, University Medical Center Groningen, Groningen, the Netherlands.
² Department of Hematology, HOVON Data Center, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
³ Department of Oncology, University Hospital, Inselspital, and University of Bern, Bern, Switzerland.
⁴ Department of Internal Medicine, Meander Hospital Amersfoort, Amersfoort, the Netherlands.
⁵ Department of Hematology, Oncology Institute of Southern Switzerland, Ospedale Regionale, Bellinzona, Switzerland.
⁶ Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius University, Vilnius, Lithuania.
⁷ Department of Hematology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
⁸ Department of Hematology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, the Netherlands.
⁹ Department of Hematology, ZNA Stuivenberg/Middelheim, Antwerp, Belgium.
¹⁰ Department of Hematology, Hagaziekenhuis, Den Haag, the Netherlands.
¹¹ Department of Hematology, Amphia Hospital, Breda, the Netherlands.
¹² Department of Medical oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
¹³ Department of Hematology, Medical Center Leeuwarden, Leeuwarden, the Netherlands.
¹⁴ Department of Medical Oncology and Hematology, Universitätsspital Zurich, Zurich, Switzerland.
¹⁵ Department of Hematology, Antonius Hospital, Nieuwegein, the Netherlands.
¹⁶ Department of Hematology, Isala Hospital, Zwolle, the Netherlands.
¹⁷ Department of Hematology, AZ Delta Roeselare, Roeselare, Belgium.
¹⁸ Department of Internal Medicine, Division of Hematology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands.
¹⁹ Department of Hematology, Medical Spectrum Twente, Enschede, the Netherlands.
²⁰ Department of hematology, Maxima Medical Center, Veldhoven, the Netherlands.
²¹ Division of hematology, University Hospital Genève and Faculty of Medicine, University of Genève, Genève, Switzerland.
²² Service and Central Laboratory of Hematology, Department of Oncology and Department of Laboratory Medicine and Pathology, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
²³ Department of Hematology, University Medical Center Groningen, Groningen, the Netherlands. [email protected].

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

Decitabine