General Patient-Reported Outcome Measure Tools Non-Reflective of AL Amyloidosis Quality of Life (QoL): A Systematic Literature Review

Abstract

Background: Systemic AL Amyloidosis is characterized by deposition by amyloid fibrils of light chains produced by clonal plasma cells. New combination therapies have substantially prolonged the life expectancy of patients with AL Amyloidosis . Still the prognosis of the disease in the majority of the patients is dismal and Quality of Life (QoL) issues should be included in clinicians' primary objectives. Nowadays, patient-reported outcome measures (PROMs) are considered one of the most responsive tools that can guide personalized interventions to optimize QoL in parallel with therapeutic interventions. The aim of this metanalysis was to establish which PROMs have been utilized in studies on AL Amyloidosis and evaluate their validity.Methods: Two independent investigators (S.B.; C.K.) systemically reviewed PubMed, Medline and EMBASE databases for publications up to May 2021 on PROMs employed to report QoL outcomes in AL Amyloidosis. The identified PROMs were subsequently assessed for their validity in this context against COSMIN (Consensus-based Standards for the selection of health Measurement Instruments) quality criteria.Results:Of the 246 publications originally retrieved, only 57 were further analysed as 92 were duplicates, 11 were irrelevant to AL Amyloidosis, 56 did nor refer to QOL and 13 reported QOL without using QOLQs, 13 were case-reports and 4 were review articles. These included 47 observational studies and 10 prospective clinical trials. In these, thirteen different PROMs were used on occasion to report QOL outcomes (SF-36; EQ-5D-3L; FACT-G; PROMIS-GH); HPRSS; DT; EORTC QLQ-C30; KCCQ-12; GAF; SWLS; STAI; CESD; MDASI) with SF-36 being the most popular (35/ 58 publications). All of them are traditionally validated in similar to AL Amyloidosis diseases (e.g. Multiple Myeloma) or in its complications (e.g. Congestive Heart Failure). In the absence of face-validity studies, the content validity of these PROMs was assessed against QOL aspects identified in literature by open questionnaires (Table 1). The outcome of the intensive analysis of these studies showed that the QoLQ fail to cover the broad spectrum of disease symptoms and current therapy-related toxicity. Furthermore, there is limited if any evidence for the validation of these tools in this context (Table 2). COSMIN criteria were met only for SF-36 and PROMIS-GH as regards internal consistency (Cronbach's a>70).Conclusions: This literature review reveals that commonly applied PROMs in studies on AL Amyloidosis do not represent the impact of this complex disease and its treatment on QoL issues. Thus, there is a need to develop a new, well-validated, disease-specific PROM that can facilitate the approval of new treatments and the adjustment of therapy-intensity according to its toxicity and QoL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.