Development and validation of a disease-relevant patient-reported outcome tool in light chain amyloidosis

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ABSTRACT Light chain amyloidosis (AL) is a plasma cell disorder characterized by organ dysfunction from insoluble fibril deposition derived from clonal light chains. The disease is associated with high early mortality and is treated with chemotherapies similar to multiple myeloma. Decline in health status is predominant in AL and often the signature feature at presentation. Even when chemotherapy produces a successful hematologic response, patients may continue to experience symptoms related to organ (e.g. cardiac, renal, neurologic) dysfunction, due to deposition of fibrils prior to therapy. Therefore, measurement of PROs, such as patient-reported fatigue and physical functioning, is a critical, yet underutilized, aspect of the overall outcomes assessment of trials of AL therapies. The candidate for this mentored patient-oriented research career development (K23) award, Dr. Anita D'Souza, is a hematology/oncology trained amyloid specialist with demonstrated success in conducting investigator-initiated clinical trials. As the Scientific Director of the Plasma Cell Disorders Working Committee in the NIH-funded Center for International Blood and Marrow Transplant Research and member of the Data and Coordinating Center for the NIH-funded Blood and Marrow Transplant Clinical Trials Network, Dr. D'Souza is well positioned for a career in developing and executing clinical trials in plasma cell disorders. Her career goal is to conduct patient-centered amyloid clinical research, where the patient's perspective is a standard and expected component of clinical trials 1) evaluating new treatments for AL amyloidosis and 2) using PROs for symptom monitoring and management . To accomplish this goal, Dr. D'Souza requires didactic training and mentorship in PRO methodology, mentorship in patient-centered research, and mentorship in effective engagement with patients and patient advocates. In this K23 application, and in the context of providing this training and mentorship, we propose to develop and evaluate a PRO tool relevant for AL (the AL-PROfile), utilizing items from the library of NIH PROMIS measures. Specific Aim 1 will determine the most relevant symptom and functioning domains for patient-centered AL research through literature review and qualitative interviews with patients, patient advocates, and clinical and research experts, select items from the PROMIS item libraries to comprise the AL-PROfile, and confirm item comprehension in cognitive interviews with patients; Aim 2 will evaluate the psychometric measurement properties of the AL-PROfile, including convergent and discriminant validity, known groups validity, internal consistency, test-retest reliability, and responsiveness to change; and Aim 3 will track PROs longitudinally in newly diagnosed patients in clinical care. Dr. D'Souza's training plan incorporates didactics, mentoring by a multi-disciplinary team, and research experience that will allow her to augment her expertise in AL clinical trials with a deeper understanding of patient-centered research and PROs. The work will provide preliminary data to support an R01 proposal to conduct a randomized, multicenter clinical trial to test the AL-PROfile as an intervention for symptom management in AL .