Quality of Life in Elderly Patients with Acute Myeloid Leukemia Undergoing Induction Chemotherapy
Authors: Oliva Esther Natalie , Salutari Prassede , Candoni Anna , Freyrie Alessandra , Capelli Debora , Di Raimondo Francesco , Volpe Antonio , Cascavilla Nicola , Di Bartolomeo Paolo , Simeone Erica , Cortelezzi Agostino , Leoni Pietro , Musto Pellegrino , Morabito Fortunato , Niscola Pasquale , Ranieri Natale , Santacaterina Irene , Marino Antonio Giovanni , Cufari Patrizia , Alati Caterina , Ronco Francesca 
Published: October 2019

Abstract
Aims: In elderly patients with acute myeloid leukemia (AML), complete remission (CR) rate following intensive chemotherapy is approximately 45%, considerably lower than in younger patients, with a shorter duration of remission and high treatment-related mortality (30-50%). Median survival is about 12 months. Intensive chemotherapy is indicated in a small proportion of "fit" elderly patients. In a phase III, prospective, randomized, open-label, multicenter trial designed to assess the efficacy of post-remission treatment with 5-Azacitidine versus best supportive care (BSC) in patients > 60 years of age with AML in CR after conventional induction ("3+7") and consolidation chemotherapy, quality of life (QoL) was assessed from diagnosis. We present interim results of changes of QoL.
Methods: Patients with newly diagnosed AML with > 30% myeloid marrow blasts, either "de novo" or evolving from myelodysplastic syndrome without contraindications for intensive chemotherapy and with an ECOG performance status < 3 are included. Induction chemotherapy consists of two courses of "3+7": Daunorubicin 40 mg/m2 daily days 1-3 and cytarabine 100 mg/m2 daily continuous IV infusion days 1-7. Patients in CR receive consolidation (cytarabine 800 mg/m2 3 hour infusion bid days 1-3) and are randomized 1:1 to receive BSC or 5-Azacitidine maintenance therapy up to 4 years and six months until AML recurrence. QoL assessment was performed using the EORTC QLQ-C30 and the QOL-E v.3 questionaires.
Results: QoL results assessed at 3 time points are reported: 1) baseline; 2) at hematological recovery immediately after the first "3+7" course; and 3) after consolidation at randomization. Ninety-nine patients (male/female 50/49) of median age 70 (IQR 65-74) years have been enrolled. At diagnosis, mean hemoglobin was 9.2 (SD ± 2.4) g/dL, leukocytes were 7.9 (2.3-29.6)/µL, platelet count was 54 (IQR 29-85) Gi/L and bone marrow blasts were 70 (IQR 50-85)%. Seventy-five patients had "de novo" AML. Twenty-three patients had comorbidities. Forty-three patients had an ECOG PS 1 and 28 had ECOG PS 2. Baseline median QOL-E scores were poor (≤60) in all dimensions, except for fatigue (76, IQR 52-85). EORTC QLQ-C30 confirmed that fatigue was not prevalent at diagnosis (median 33, IQR 22-56). Median baseline EORTC QLQ-C30 scores were good in all domains except for global health status (GHS, median 50, IQR 33-67). Gender, comorbidities, bone marrow blasts and secondary AML were not related to QoL. Baseline Hb levels correlated with QOL-E functional (r=0.0216, p=0.14), fatigue (r=0.256, p=0.002) and disease-specific (r=0.247, p=0.010) scores and with EORTC QLQ-C30 GHS (r=0.270, p=0.001), physical (r=0.304, p<0.0001), role (r=0.281, p=0.001), cognitive (r=0.262, p=0.003), social (r=0.229, p=0.010) functions and fatigue (r=-0.280, p=0.001), dyspnea (r=-0.287, p=0.001) and appetite loss (r=0.244, p=0.007). Age correlated with QOL-E disease specific scores (r=0.242, p=0.012). There were no changes in QOL-E scores following 1st "3+7". However, the EORTC QLQ-C30 detected deterioration in physical function from median 80, IQR 60-93, to 67, IQR 52-87 (p=0.008), in role function from median 83, IQR 67-100, to 67, IQR 33-83 (p=0.023) and in GHS from median 50, IQR 33-69, to 67, IQR 50-75 (p=0.002) and improvement in dyspnea (p=0.023). Forty patients obtained a CR. Interestingly, baseline role function was better (median 83, IQR 67-100) in cases obtaining a CR than in resistant patients (median 67, IQR 33-83, p=0.007). Patients obtaining CR experienced improvements after consolidation in median QOL-E physical scores from 56, IQR 41-72 to 63, IQR 50-84 (p=0.033), disease-specific domain scores from 59, IQR 48-67 to 74, IQR 67-85 (p=0.003) and treatment-outcome index scores from 55, IQR 32-77, to 79, IQR 41-86 (p=0.026). Median EORTC QLQ-C30 emotional function improved after consolidation therapy from 83, IQR 67-92, to 92, IQR 77-100 (p=0.015) as well as GHS from median 50, IQR 33-65 to 67, IQR 58-83 (p=0.002). Dyspnea and insomnia regressed while financial problems increased.
Conclusions: Elderly patients with AML at diagnosis identified as fit for chemotherapy generally do not present fatigue, though health status is poor and is mainly correlated with Hb levels. Role function may predict response to induction chemotherapy. Patients obtaining CR perceive improvements in global health, including physical and emotional QoL and symptoms.

Disclosures
Oliva: Celgene: Other: Advisory Board, Speakers Bureau; Amgen: Consultancy; Novartis: Speakers Bureau.