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535 10-Day Decitabine Versus Intensive Chemotherapy Followed By Transplantation in Fit AML Patients Aged ≥60 Years: Health-Related Quality of Life Outcomes of the Randomized Phase III Trial AML21 of the EORTC Leukemia Group, Gimema, Celg, and Gmds-SG

Program: Oral and Poster Abstracts
Type: Oral
Session: 613. Acute Myeloid Leukemias: Clinical and Epidemiological: Long-term Outcomes in Clinically Defined Subgroups of Patients with Acute Myeloid Leukemia
Hematology Disease Topics & Pathways:
Research, Acute Myeloid Malignancies, AML, Clinical Research, patient-reported outcomes, Diseases, Myeloid Malignancies
Sunday, December 11, 2022: 12:00 PM

Fabio Efficace, PhD1*, Gerwin A. Huls, MD, PhD2, Michal Kicinski3*, Walter JFM Van Der Velden4, Richard Noppeney, MD5*, Sylvain Chantepie, MD6*, Laimonas Griskevicius, MD, PhD7*, Andreas Neubauer, MD8, Ernesta Audisio9*, Mario Luppi10*, Stephan Fuhrmann, M.D.11*, Robin Foà12*, Martina Crysandt, MD13*, Gianluca Gaidano, MD, PhD14, Radovan Vrhovac, MD, PhD15*, Adriano Venditti, MD16, Eduardus F.M. Posthuma, MD, PhD17, Anna Candoni, MD18*, Frederic Baron19, Olivier Legrand, MD, PhD20*, Andrea Mengarelli, MD21*, Marco Vignetti, MD1*, Anne Giraut, PhD3*, Corneel Coens3*, Stefan Suciu3*, P.W. Wijermans22 and Michael Luebbert, MD23

1Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy
2University Medical Center Groningen, Groningen, Netherlands
3EORTC Headquarters, Brussels, Belgium
4Department of Hematology, Radboud University Medical Centre, Nijmegen, Netherlands
5Klinik für Hämatologie, Universitätsklinikum Essen, Essen, Germany
6Institut d’Hématologie de Basse Normandie, Centre Hospitalier Universitaire de Caen, Caen, France
7Department of Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius University, Vilnius, Lithuania
8Hematology, Oncology, Immunology, Philipps University, Marburg, Germany
9SC Ematologia Città della Salute e della Scienza Torino, Torino, Italy
10Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria, Modena, Italy
11Department of Hematology and Oncology, HELIOS Hospital Berlin-Buch, Berlin, Germany
12Ematologia, Dipartimento di Medicina Traslazionale e di Precisione, "Sapienza" Università di Roma, Rome, Italy
13Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, Center for Integrated Oncology Aachen Bonn Cologne, Duesseldorf (CIO ABCD), Aachen, Germany
14Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carità, Novara, Italy
15Department of Haematology, University Hospital Centre Zagreb, Zagreb, Croatia
16Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
17Department of Internal Medicine, Reinier de Graaf Hospital, Delft, Netherlands
18Clinica Ematologica Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy
19University of Liege, Liege, Belgium
20Service d'Hématologie Clinique et de Thérapie cellulaire, Hôpital Saint Antoine, APHP, Paris, France
21USOD Ematologia e Trapianti, IRCSS Istituto Nazionale Tumori Regina Elena, Roma, Italy
22Department of Hematology, Haga Teaching Hospital, The Hague, Netherlands
23Department of Hematology, Oncology, and Stem-Cell Transplantation, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany

Background

To assess the optimal treatment strategy for fit older patients with acute myeloid leukemia (AML), we performed a large international phase III randomized controlled trial (RCT) in fit AML patients aged >60 years, comparing 10-day decitabine (DEC) followed by allografting (HSCT) versus intensive chemotherapy (IC, “3+7” regimen) followed by HSCT. This trial revealed comparable HSCT rates and survival outcomes, but a more favorable safety profile with DEC when compared to IC (Lübbert M. et al, HemaSphere, 6, 26-27, 2022), supporting the hypothesis that reduced toxicity translates into a better health-related quality of life (HRQoL).

Objective

We hereby report the HRQoL outcomes of this international RCT.

Patients and Methods

HRQoL was a secondary endpoint and was assessed by the EORTC QLQ-C30 and its validated module for evaluating HRQoL in older patients, namely the EORTC QLQ-ELD14. Key inclusion criteria were: newly diagnosed AML, age >60 years, eligibility for IC, and a WHO performance status of ≤2. Assessments of HRQoL were performed at baseline and then at 2 (at regeneration after two treatment cycles), 6 and 12 months. For patients undergoing a HSCT, HRQoL was assessed prior to the procedure and at day 100 after the transplant. Quality of life deterioration (QD) was defined as any of the following events: death, progression, and clinically meaningful deterioration from baseline in at least one of the five pre-selected primary HRQoL scales (i.e., physical functioning, role functioning, fatigue, pain, and illness burden). The two co-primary endpoints were: QD at 2 months and QD at 6 or 12 months. A difference of 10 points or more was considered clinically meaningful. We hypothesized better HRQoL outcomes for patients treated with DEC. The changes in the primary HRQoL scales from baseline to 2 months and from baseline to the average of 6 and 12 months were secondary HRQoL endpoints. HRQoL trajectories of patients undergoing HSCT on-study based on evaluations at baseline, prior to HSCT and at day 100 after HSCT were also described. This study was registered at ClinicalTrials.gov (NCT02172872).

Results

Between December 2014 and August 2019, 606 patients were randomized and a baseline HRQoL assessment was available for 549 patients (91%): 279 out of 303 in the DEC arm and 270 out of 303 in the IC arm. Compliance among alive patients at 2, 6 and 12 months was 57%, 57%, and 64%, respectively. The proportion of patients evaluable for QD at 2 months was 60%. The proportion of patients evaluable for QD at 6 or 12 months was 82%.

Analysis of the primary HRQoL endpoint showed that the proportion of patients deteriorating at 2 months was 76% (95% CI, 69 to 82%) in the DEC group vs 88% (95% CI, 82 to 93%) in the IC group (odds ratio 0.43 [95% CI, 0.24 to 0.76], P=.003). Several sensitivity analyses, using multiple imputation to deal with missing values and predefined modifications of the definition of QD, confirmed this finding. QD analysis at 6 or 12 months indicated no statistically significant difference between both arms (odds ratio 0.83 [95% CI, 0.46 to 1.52]).

At 2 months from randomization, the illness burden scale increased by 4.19 (95% CI, -0.44 to 8.83) points in the DEC and by 15.15 (95% CI, 9.88 to 20.42) points in the IC arm, indicating a clinically meaningful and statistically significant difference of -10.96 (95% CI, -17.94 to -3.97), P=.004. The changes in the primary HRQoL scales from baseline to 2 months and from baseline to the average of 6 and 12 months are presented in Table 1.

Baseline data were available for 218 of the 240 patients who received an on-study HSCT. Clinically meaningful HRQoL deteriorations between baseline and post-HSCT in the IC group were observed in all primary HRQoL scales except for pain. The change from baseline to post-HSCT HRQoL in the DEC arm appeared less pronounced and did not reach the threshold of clinical relevance.

Conclusions

Following two months of treatment, there was a significantly lower percentage of patients treated with DEC who reported HRQoL deterioration, compared to those treated with IC. Additionally, patients treated with DEC did not experience any clinically meaningful deterioration in key pre-specified HRQoL domains post-HSCT, while this was the case for patients treated with IC.

Disclosures: Efficace: Incyte: Consultancy; Novartis: Consultancy, Research Funding; Janssen: Consultancy; Abbvie: Consultancy, Research Funding; Syros: Consultancy. Kicinski: MSD, Pierre Fabre, BMS, Janssen: Research Funding. Griskevicius: Miltenyi Biomedicine: Membership on an entity's Board of Directors or advisory committees. Luppi: Gilead sci: Other: Travel grant; Abbvie, Jazz Pharma, Gilead sci, MSD, Novartis, Sanofi, Daiichi-Sankyo, Grifols: Membership on an entity's Board of Directors or advisory committees. Fuhrmann: Amgen, Sanofi, GSK, Gilead Sci, Roche and Janssen: Other: Advisory Board. Crysandt: Pfizer: Honoraria; Astra Zeneca: Honoraria; Novartis: Honoraria. Gaidano: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vrhovac: Abbvie, Astellas, Pfizer, Pharmas: Consultancy; Abbvie, Astellas, MSD, Novartis, Pfizer, Pharmas, Servier, Teva: Speakers Bureau. Venditti: Medac: Consultancy; Jazz Pharmaceuticals: Honoraria, Research Funding; Janssen & Cylag: Honoraria; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; astrazeneca: Honoraria; abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees. Candoni: Celgene, Abbvie, Pfizer, Janssen, Astellas, Jazz, Gilead, Incyte, Amgen: Other: Speaker honoraria. Baron: Celgene, Abbvie, Novartis, Pfizer: Other: Travel grant; Abbvie and Sanofi: Other: Speaker honoraria. Vignetti: IQVIA, Dephaforum, AbbVie, Astrazeneca: Speakers Bureau. Luebbert: AbbVie: Honoraria; Astex: Honoraria; Janssen: Research Funding; Otsuka: Consultancy; Syros: Consultancy; Cheplapharm: Other: study drug.

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