The Reporting, Use, and Validity of Patient-Reported Outcomes in Multiple Myeloma in Clinical Trials: A Systematic Literature Review

Abstract

Background: Patient-reported outcomes (PROs) are becoming increasingly important in supporting clinical outcomes in clinical trials. In multiple myeloma (MM), PRO measurement is useful to reveal how treatment affects physical, psychosocial, and functional behaviour as well as symptoms and treatment-related adverse events to evaluate the benefit-risk ratio of a particular drug or drug combination. We report the types of PRO instruments used in MM, the frequency in which they are utilised in randomised controlled trials (RCTs), and the consistency of their reporting. Methods: The European Hematology Association (EHA) supports the development of guidelines for the use of PROs in adult patients with haematological malignancies. The first step is the present systematic review of the literature. MEDLINE and CENTRAL were searched for RCTs in MM between 2015 and 2020. Study design, characteristics of MM and its treatment, the primary outcomes, and the types of PRO instrument(s) were extracted using a predefined template. Additionally, in a stepwise approach, it was assessed whether the identified instruments had been validated for multiple myeloma patients, patients with haematological malignancies, or cancer patients. Results: Following screening for RCTs, 283 studies were included for review from 10,707 records retrieved, and 118 of these planned the use of PRO measures. Thirty-eight PRO instruments were reported. The most frequently used instrument (92 studies) was the EORTC QLQ-30. The EORTC-MY20 MM-specific questionnaire was the second most frequently used (50 studies), together with the EQ-5D (50 studies). Only 19 PRO instruments reported were consistent with the trial registry. Furthermore, in 58 publications, the information on PRO instruments differed between the publication and the trial registry. Further, information on PRO in HTA reports was available for 26 studies, of which 18 reports were consistent with the trial registries. Out of the 38 instruments used, six had been validated for patients with multiple myeloma (the most frequently used), six for patients with haematological malignancies, and 10 for cancer patients in general. Conclusions: The findings indicate that the measurement of PROs in RCTs for MM is underutilised, underreported, and often inconsistent. Guidelines for the appropriate use of PROs in MM are needed to ensure standardisation in selection and reporting. Furthermore, not all PRO instruments identified have been validated for myeloma patients or patients with haematological malignancies. Thus, guidelines for the appropriate use and reporting of PROs are needed in MM to ensure standardisation in the selection and reporting of PROs.

The EASEMENT study: A multicentre, observational, cross‐sectional study to evaluate patient preferences, treatment satisfaction, quality of life, and healthcare resource use in patients with multiple myeloma receiving injectable‐containing or fully oral therapies

“…In MM, as for many diseases, PROs have become an increasingly important tool to support clinical outcomes, and help guide clinicians towards tailoring treatment to their patients' needs and lifestyles. 15,16 The EASEMENT study aimed to determine satisfaction with, and preference of, the treatment received, treatment patterns, and resource use, stratified by both route of administration (orals vs. injectables) and MM status in patients who had received ≥1 cycle of their current line of therapy at the index date.…”

“…1,12 While oral therapies offer the potential for greater convenience versus conventional injectable regimens, 13,14 data on patient-reported outcomes (PROs) such as patient preferences, QoL, and healthcare utilisation, have only recently started to be reported. [15][16][17][18][19][20] Receiving injectable treatment usually requires hospital visits and administration by a healthcare provider 16 ; several recent studies identified oral medication as an important factor for patients with MM, based on greater perceived treatment convenience, less impairment of daily activities and work productivity. [16][17][18][19][20] However, there are limited data about patient perspectives, experiences, and expectations of their MM treatment 21 or when patients switch from injectable to oral therapies.…”

Impact of elranatamab on quality of life: Patient‐reported outcomes from MagnetisMM‐3

“…[1][2][3][4] Bone lesions, bone marrow and renal failure, and immunodeficiency contribute to many complications of the disease. 4 Advances in anti-myeloma treatments have improved disease response rates and patient life expectancy; however, they are accompanied by multiple side effects, most commonly infections and neurological, haematopoietic and cardiac toxicities, which can impact patient QOL. [4][5][6][7] Moreover, health-related QOL deteriorates with each subsequent relapse and line of therapy.…”

“…4 Advances in anti-myeloma treatments have improved disease response rates and patient life expectancy; however, they are accompanied by multiple side effects, most commonly infections and neurological, haematopoietic and cardiac toxicities, which can impact patient QOL. [4][5][6][7] Moreover, health-related QOL deteriorates with each subsequent relapse and line of therapy. 5 Thus, treatment goals for patients with relapsed or refractory multiple myeloma (RRMM) should also include managing disease and treatmentrelated symptoms to maintain or potentially improve their QOL in addition to extending their survival.…”

“…4 For MM in particular, PRO assessments can be used to measure patient experience with physical, psychological and functional symptoms that may not otherwise be captured by clinician-reported symptomatic adverse events. 4,8,9 In a recent analysis of 238 MM clinical trials, 49.6% of studies planned the use of PROs, with the most common being the European…”