Patient-Centered Evaluation of Clinical Benefit in Acute Myeloid Leukemia: Importance of Early Engagement with Patients
Authors: Bell Jill A. , Pompilus Farrah Anne , Rams Alissa , Zhu Yanyan , Ciesluk Anna , Bejar Rafael , Fram Robert J. , Faller Douglas V. , Marquis Patrick 
Published: November 2019

INTRODUCTION
Acute myeloid leukemia (AML), the most common form of acute leukemia among adults, is characterized by proliferation of immature myeloid cells in the peripheral blood, bone marrow, and/or other tissues, resulting in cytopenias. Clinical features such as anemia cause fatigue and dyspnea, which may negatively impact health-related quality of life, emphasizing the need for patient-centered outcomes to evaluate new therapies. Patients are uniquely positioned to inform the understanding of the therapeutic context for clinical development and provide additional information not captured by traditional clinical measures. Understanding the AML patient experience is essential for selecting relevant patient-reported outcome (PRO) measures.
The purpose of this research was to incorporate the patient voice and generate an evidence base for selecting PRO endpoints for assessing clinical benefit.
METHODS
A cross-sectional, qualitative study was implemented among AML patients identified through clinical recruitment agencies and a patient advocacy organization. A targeted literature review (PubMed, Jan '00-Feb '19) and expert clinician consultation were conducted to explore the clinical perspective on treatment and observed patient experience. Following approval from an independent review board, qualitative concept-elicitation interviews were conducted with AML patients using a semi-structured interview guide. Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and items from the EORTC item library; items were selected based on previous research in patients with myelodysplastic syndromes.
All interviews were audio-recorded, transcribed, and analyzed thematically using inductive coding targeting manifestations of symptoms and impacts. To ensure enough patients were interviewed, saturation was assessed based on the number of new codes emerging in the data.
RESULTS
Patients were 63 (±6.3) years old; 65% female; 80% white; 75% retired; 95% married. Half were diagnosed within the last 6 months and 25% within 7-12 months of the interviews. Approximately 60% of patients were receiving treatment. Eastern Cooperative Oncology Group status (range: 0, fully active without restriction to 4, completely disabled and confined to bed or chair) was reported by patients (0=5%; 1=25%; 2=35%; 3=30%; 4=5%).
A wide range of symptoms was reported by patients; among the most frequent were tiredness, general fatigue, lack of energy, shortness of breath on exertion, weakness, dizziness or lightheadedness, bruising, bleeds (nose/gums), body aches/pain, fever, night sweats, constipation, and diarrhea (Figure).
The following themes emerged from the analysis of symptom-related codes: fatigue, shortness of breath, dizziness, bleeding, general malaise/pain, and gastrointestinal issues.
Patients reported a wide range of impacts on their daily lives, which included having to stay in bed/chair/couch, difficulty walking, difficulty lifting heavy objects, moving slowly, needing to take breaks, napping/sleeping during the day, not getting restful sleep, needing to lie down, difficulty doing various activities (e.g., driving, shopping, preparing food, doing yardwork, laundry), spending less time with family/friends or caring for yourself/others, depressed mood, worry, and having to be careful/mindful of risk of infection.
The following main themes emerged from the analysis of impact-related codes: daily life functioning, leisure activities, physical mobility, sleep, social limitations, and psychological impact. Other themes that were reported by patients included appearance, cognition, and work (Figure).
Debriefing results indicated that all patients comprehended the EORTC items tested and confirmed their relevance.
CONCLUSIONS
Direct patient engagement via qualitative research and thematic analysis provided a valuable evidence base to inform the selection of conceptually relevant PRO measures. The themes suitable for inclusion in clinical programs should be further discussed.
Based on this research, the EORTC QLQ-C30 is a reasonable instrument for use in patients with AML. Early involvement of patients allows for potential inclusion of supplemental symptom and impact items from the EORTC Item Library in clinical programs to improve conceptual coverage of the patient experience.

Disclosures
Bell: Takeda Pharmaceuticals: Employment, Equity Ownership. Pompilus:Takeda Pharmaceuticals: Research Funding; Modus Outcomes: Employment. Rams:Modus Outcomes: Employment; Takeda Pharmaceuticals: Research Funding. Zhu:Takeda Pharmaceuticals: Employment. Ciesluk:Modus Outcomes: Employment; Takeda Pharmaceuticals: Research Funding. Bejar:Celgene: Consultancy; Takeda Pharmaceuticals: Research Funding; AbbVie/Genentech: Consultancy, Honoraria; Astex/Otsuka: Consultancy; Modus Outcomes: Consultancy; Daiichi-Sankyo: Consultancy. Fram:BeyondSpring Pharmaceuticals, Inc.: Consultancy; Takeda Pharmaceuticals: Employment. Faller:Boston University: Employment; Phoenicia Biosciences: Equity Ownership; Viracta Pharmaceuticals: Equity Ownership; Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment; Briacell Pharmaceuticals: Equity Ownership. Marquis:Takeda Pharmaceuticals: Research Funding; Modus Outcomes: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.