ROLE OF FUNCTIONAL PARAMETERS IN ELDERLY AML PATIENTS DEEMED UNFIT FOR INDUCTION CHEMOTHERAPY: RESULTS FROM THE DECIDER TRIAL
Author(s): ,
Valerie Hupfer
Affiliations:
Department of Medicine I, Hematology, Oncology and Stem Cell Transplantation,University Hospital Freiburg, Faculty of Medicine, University of Freiburg,Freiburg,Germany
,
Claudia Schmoor
Affiliations:
Clinical Trials Unit,University Hospital Freiburg, Faculty of Medicine, University of Freiburg,Freiburg,Germany
,
Richard F. Schlenk
Affiliations:
Department of Internal Medicine III, Hematology, Oncology, Palliative Medicine, Rheumatology and Infectious Dieseases,University Hospital Ulm,Ulm,Germany
,
Helmut R. Salih
Affiliations:
Department of Internal Medicine II, Oncology, Haematology, Immunology, Rheumatology and Pulmology,University Hospital Tuebingen, Eberhard-Karls-Universität Tuebingen,Tuebingen,Germany
,
Martina Crysandt
Affiliations:
Department of Internal Medicine IV, Hematology, Oncology, Hemostaseology and Stem Cell Transplantation,RWTH Aachen University Hospital,Aachen,Germany
,
Michael Heuser
Affiliations:
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Hannover Medical School,Hannover,Germany
,
Hans-Walter Lindemann
Affiliations:
Department of Hematology and Oncology,Catholic Hospital Hagen,Hagen,Germany
,
Carsten Müller-Tidow
Affiliations:
Department of Internal Medicine V,University Hospital Heidelberg,Heidelberg,Germany
,
Gesine Bug
Affiliations:
Department of Medicine II, Hematology and Oncology,University Hospital Frankfurt,Frankfurt,Germany
,
Ulrich Germing
Affiliations:
Department of Hematology, Oncology and Clinical Immunology,Heinrich-Heine-University,Düsseldorf,Germany
,
Katharina S. Götze
Affiliations:
Department of Internal Medicine III,Klinikum rechts der Isar, Technische Universität München,München,Germany
,
Carsten Schwänen
Affiliations:
Department of Hematology, Oncology and Palliative Medicine,Ortenau Hospital Offenburg,Offenburg,Germany
,
Sebastian Scholl
Affiliations:
Department of Internal Medicine II, Hematology and Oncology,University Hospital Jena,Jena,Germany
,
Aristoteles Giagounidis
Affiliations:
Department of Oncology, Hematology and Palliative Care,Marienhospital Düsseldorf,Düsseldorf,Germany
,
Andreas Neubauer
Affiliations:
Klinik für Innere Medizin, Schwerpunkt Hämatologie, Onkologie und Immunologie,Philipps Universität Marburg,Marburg,Germany
,
Jürgen Krauter
Affiliations:
Department of Internal Medicine III,Municipal Hospital of Braunschweig,Braunschweig,Germany
,
Arnold Ganser
Affiliations:
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Hannover Medical School,Hannover,Germany
,
Hartmut Döhner
Affiliations:
Department of Internal Medicine III, Hematology, Oncology, Palliative Medicine, Rheumatology and Infectious Dieseases,University Hospital Ulm,Ulm,Germany
,
Björn Hackanson
Affiliations:
Department of Internal Medicine II,University Hospital of Augsburg,Augsburg,Germany
,
Gabriele Ihorst
Affiliations:
Clinical Trials Unit,University Hospital Freiburg, Faculty of Medicine, University of Freiburg,Freiburg,Germany
Michael Lübbert
Affiliations:
Department of Medicine I, Hematology, Oncology and Stem Cell Transplantation,University Hospital Freiburg, Faculty of Medicine, University of Freiburg,Freiburg,Germany
EHA Library. Hupfer V. 06/12/20; 294216; EP1736
Ms. Valerie Hupfer
Ms. Valerie Hupfer
Contributions
Abstract

Abstract: EP1736

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background

In older AML patients (pts), besides specific biological characteristics, functional parameters (pmt) and patient-reported symptoms have an impact on disease course. The prognostic value of this approach on overall survival (OS) has been demonstrated with special emphasis on fatigue (Klepin et al., Blood 2013, Lacourt et al., Oncotarget 2018). 

Aims

Within the DECIDER trial (AMLSG 14-09, NCT00867672) we assessed pmt informing the shared-decision making process against induction chemotherapy (IC). We also aimed at validation of a Frailty Score consisting of performance status (PS), activities of daily living (ADL) and fatigue predicting OS, previously established in a cohort of 107 elderly AML/MDS pts treated with hypomethylating agents (HMAs, Deschler et al., Hematologica 2013). 

Methods

In the DECIDER trial 200 non-fit AML pts aged >60 years (yr) were randomized between 4 treatment arms to investigate the efficacy and safety of valproic acid (VPA) and ATRA in combination with decitabine. Reasons to recommend study treatment rather than IC were systematically captured. For the Frailty Index validation, pretreatment PS (ECOG), ADL (Barthel index) and fatigue (EORTC QLQ-C30) were assessed in 200, 175 and 156 pts, respectively. Pts with missing ADL and/or fatigue assessments tended to have lower PS than those with complete data, in part explaining why the assessments could not be performed. Cox regression models were used to calculate the prognostic value of the single factors and the Frailty Score on OS.

Results

Regarding the reasons for the mutual decision against IC at least one of the following conditions was indicated:reduced PS (EOCG ≥3), comorbidities (HCT-CI ≥3), prior hematologic disorder, reduced ADLs, or increased fatigue in 179 pts. Of the remaining 21 pts, 10 were aged ≥75 yr, and in the remaining 11 pts reasons stated were: adverse cytogenetics (2 pts), patient wish (6 pts), or no obvious reason identified (3 pts). Complete data regarding the Frailty Score were available for 141 pts. Median follow-up time was 28 months and 122 pts had died. Median age at diagnosis was 76 yr and 68% of the pts were male. The median white blood count was 3100/µl, median peripheral blast count 48%, median platelet count 49.000/µl and median hemoglobin level 9.2 g/dl. 56.7% of pts had relevant comorbidities (HCT-CI≥3). ECOG PS was 0 in 19%, 1 in 61% and 2-3 in 20% of pts. 31.4% had an Barthel Index <100% and in 58.3% fatigue ≥50 on the EORTC QLQ-C30 fatigue scale was registered. Summing up these parameters and calculating the Frailty score, this resulted in 45 (31.9%) pts with a score of 0, 61 (43.3%) with a score of 1, 18 pts (12.8%) with a score of 2 and 17 (12.1%) with a score of 3. When adjusted to treatment, ECOG >1, ADL <100% and fatigue ≥50 each showed significant adverse effects on OS, with estimated HRs of 1.78, 1.91, and 1.62, respectively (Table 1). Pts can be divided into 3 risk groups (combining pts with score 2 and 3 into one group) with distinct OS, especially between group 0 and the others (adjusted for treatment, p<0.0001, Figure 1).

Conclusion

We provide a systematic assessment of patient- and disease-related factors (e.g. cytogenetics) informing the therapy decision process in older and unfit AML pts against IC. Our Frailty Score, applied to this validation cohort, divided pts into 3 distinct risk categories with significantly different OS. These results emphasize the emerging roles of ADL and fatigue as predictors of outcome beside the already well-established role of PS.

Session topic: 35. Quality of life, palliative & supportive care, ethics and health economics

Keyword(s): AML, Elderly, Fatigue, Prognostic factor

Abstract: EP1736

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background

In older AML patients (pts), besides specific biological characteristics, functional parameters (pmt) and patient-reported symptoms have an impact on disease course. The prognostic value of this approach on overall survival (OS) has been demonstrated with special emphasis on fatigue (Klepin et al., Blood 2013, Lacourt et al., Oncotarget 2018). 

Aims

Within the DECIDER trial (AMLSG 14-09, NCT00867672) we assessed pmt informing the shared-decision making process against induction chemotherapy (IC). We also aimed at validation of a Frailty Score consisting of performance status (PS), activities of daily living (ADL) and fatigue predicting OS, previously established in a cohort of 107 elderly AML/MDS pts treated with hypomethylating agents (HMAs, Deschler et al., Hematologica 2013). 

Methods

In the DECIDER trial 200 non-fit AML pts aged >60 years (yr) were randomized between 4 treatment arms to investigate the efficacy and safety of valproic acid (VPA) and ATRA in combination with decitabine. Reasons to recommend study treatment rather than IC were systematically captured. For the Frailty Index validation, pretreatment PS (ECOG), ADL (Barthel index) and fatigue (EORTC QLQ-C30) were assessed in 200, 175 and 156 pts, respectively. Pts with missing ADL and/or fatigue assessments tended to have lower PS than those with complete data, in part explaining why the assessments could not be performed. Cox regression models were used to calculate the prognostic value of the single factors and the Frailty Score on OS.

Results

Regarding the reasons for the mutual decision against IC at least one of the following conditions was indicated:reduced PS (EOCG ≥3), comorbidities (HCT-CI ≥3), prior hematologic disorder, reduced ADLs, or increased fatigue in 179 pts. Of the remaining 21 pts, 10 were aged ≥75 yr, and in the remaining 11 pts reasons stated were: adverse cytogenetics (2 pts), patient wish (6 pts), or no obvious reason identified (3 pts). Complete data regarding the Frailty Score were available for 141 pts. Median follow-up time was 28 months and 122 pts had died. Median age at diagnosis was 76 yr and 68% of the pts were male. The median white blood count was 3100/µl, median peripheral blast count 48%, median platelet count 49.000/µl and median hemoglobin level 9.2 g/dl. 56.7% of pts had relevant comorbidities (HCT-CI≥3). ECOG PS was 0 in 19%, 1 in 61% and 2-3 in 20% of pts. 31.4% had an Barthel Index <100% and in 58.3% fatigue ≥50 on the EORTC QLQ-C30 fatigue scale was registered. Summing up these parameters and calculating the Frailty score, this resulted in 45 (31.9%) pts with a score of 0, 61 (43.3%) with a score of 1, 18 pts (12.8%) with a score of 2 and 17 (12.1%) with a score of 3. When adjusted to treatment, ECOG >1, ADL <100% and fatigue ≥50 each showed significant adverse effects on OS, with estimated HRs of 1.78, 1.91, and 1.62, respectively (Table 1). Pts can be divided into 3 risk groups (combining pts with score 2 and 3 into one group) with distinct OS, especially between group 0 and the others (adjusted for treatment, p<0.0001, Figure 1).

Conclusion

We provide a systematic assessment of patient- and disease-related factors (e.g. cytogenetics) informing the therapy decision process in older and unfit AML pts against IC. Our Frailty Score, applied to this validation cohort, divided pts into 3 distinct risk categories with significantly different OS. These results emphasize the emerging roles of ADL and fatigue as predictors of outcome beside the already well-established role of PS.

Session topic: 35. Quality of life, palliative & supportive care, ethics and health economics

Keyword(s): AML, Elderly, Fatigue, Prognostic factor

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