AL Amyloidosis: Development Of a Conceptual Model and a Symptom Diary

Amyloidosis is a very rare blood disease characterized by the production of abnormal misfolded extracellular proteins that are deposited in body tissues or organs, leading to organ dysfunction. The most common form is systemic light chain (AL) amyloidosis. With no cure, treatment is directed at suppressing development of the abnormal protein, correcting or stabilizing organ function, and managing symptoms. Very little research has been done to assess patients’ symptoms in this disease and how they may be mitigated by available therapies.  The first objective of this study was to understand the symptoms and impact of the disease and treatment from the patients’ perspective. This insight was used to develop a comprehensive conceptual model of AL amyloidosis.  A second objective was to confirm the content of a draft amyloidosis symptom diary and provide recommendations to refine the measure.

Three data sources were included in this study: 1) A literature review using OvidSP (includes MEDLINE and Embase)using disease-specific and quality of life search terms; 2) An internet search to identify blogs (online diaries) written by patients about their disease/treatment experience; and 3) One-on-one telephone interviews with adult AL amyloidosis patients. Patients were recruited through physician referral and by the Amyloidosis Foundation. Eligible and interested patients were mailed an informed consent form and study questionnaires. Using a standardized guide, a trained interviewer conducted a concept elicitation interview to explore experiences of living with AL amyloidosis, after which the patient completed the symptom diary and underwent a cognitive debriefing interview.  The cognitive debriefing was designed to explore patient understanding of each instruction, item, and response option. Interview transcripts were coded to identify key concepts and themes emerging from the data using qualitative data analysis software, MaxQDA.

Of 270 English language abstracts identified and reviewed, 10 articles appeared to include a patient-reported outcome (PRO) measure and were selected for full review. Nine patient blogs were identified and reviewed. Symptoms identified from the literature and from patient blogs informed the development of a draft symptom measure. Ten patients participated in the concept elicitation / cognitive debriefing interviews (mean age, 61 years, SD=8; 70% male). Eight reported experience with chemotherapy, 6 reported having received a stem cell transplant, and one had received a heart transplant. Patients identified symptoms as being related to both the disease and/or treatments.  Symptoms reported by at least 30% of the sample included fatigue (100%), weakness (100%), shortness of breath (90%), neuropathy (90%), edema (100%), dizziness/lightheadedness (80%), decreased/lack of appetite (60%), diarrhea (50%), constipation (40%), and difficulty sleeping (30%). Ninety-four percent of codes had been applied by the 7^th interview, and only one new code (“heartburn”) was applied in the last interview, suggesting that key symptom concepts were identified with this sample. A conceptual model illustrating the various impacts of disease and treatment was developed.  Findings from cognitive debriefing interviews revealed that overall, patients found the diary to be straightforward and easy to complete. Most patients reported that the symptoms included in the measure adequately captured their experiences with AL amyloidosis. However, feedback suggested that certain symptoms such as swelling in the upper body, needed clarification.

A comprehensive conceptual model of symptoms and impacts of disease and treatment was developed and could be used to identify important outcomes from the patients’ perspective that should be assessed in clinical trials to capture treatment benefit.  AL amyloidosis is associated with a wide range of symptoms related to location of amyloid deposits, as well as side effects related to the treatment administered.  Despite this variability, a core set of symptoms emerged and a draft diary capturing symptoms likely to be applicable to most patients was developed. Based on the feedback from the cognitive debriefing interviews, patients found the diary to be straightforward and easy to complete.  Additional research and use in trials can provide further evidence for the validity and reliability of the diary.

Seldin:Celgene: Research Funding; Prothena: Research Funding; Amyloidosis Foundation: Membership on an entity’s Board of Directors or advisory committees. Hui:Millennium: The Takeda Oncology Company: Employment. Berg:Millennium: The Takeda Oncology Company: Employment. Lin:Millennium: The Takeda Oncology Company: Employment.