Health-Related Quality-of-Life Results From the Open-Label, Randomized, Phase III ASPIRE Trial Evaluating Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma

Abstract

Purpose To determine the effects of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) on health-related quality of life (HR-QoL) in the Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone for the Treatment of Patients With Relapsed Multiple Myeloma (ASPIRE) trial. Methods Patients with relapsed multiple myeloma were randomly assigned to receive KRd or Rd. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module were administered at baseline; day 1 of cycles 3, 6, 12, and 18; and after treatment. The Global Health Status/Quality of Life (GHS/QoL) scale and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. The percentages of responders with ≥ 5- or 15-point GHS/QoL improvement at each cycle were compared between groups. Results Baseline questionnaire compliance was excellent (94.1% of randomly assigned patients). KRd patients had higher GHS/QoL scores versus Rd patients over 18 treatment cycles (two-sided P < .001). The minimal important difference was met at cycle 12 (5.6 points) and approached at cycle 18 (4.8 points). There was no difference between groups for the other prespecified subscales from ASPIRE. A higher proportion of KRd patients met the GHS/QoL responder definition (≥ 5-point improvement) with statistical differences at cycle 12 (KRd v Rd patients, 25.5% v 17.4%, respectively) and 18 (KRd v Rd patients, 24.2% v 12.9%, respectively). Conclusion KRd improves GHS/QoL without negatively affecting patient-reported symptoms when compared with Rd. These data further support the benefit of KRd in patients with relapsed multiple myeloma.

Methodological aspects of health‐related quality of life measurement and analysis in patients with multiple myeloma

“…Multiple imputation was used to test the robustness of the PRO results in three studies (Lee et al , ; Gimsing et al , ; Waage et al , ). Other methods of exploring the missing data mechanisms or robustness of PRO data results were: confirming the results by standardized area under the curve, mixed method of repeated measures or comparing mean scores for patients with available questionnaires at follow‐up to patients with early study discontinuation (Waage et al , ; Delforge et al , ; Stewart et al , ).…”

“…The assumption for MCAR missing data mechanism could not be confirmed in the included studies, where this aspect was investigated. In the two studies where a graphical approach was used (Stewart et al , ; Leleu et al , ), a slightly different pattern of change in global quality of life score over time was found for patients dropping out earlier compared to patients staying in the study for the whole period, but the differences were not statistically significant or clinically meaningful.…”

“…The methods applied are presented in Table I. In the ASPIRE and TOURMALINE studies, a graphical approach was used to explore patterns of monotone NR (Stewart et al, 2016;Leleu et al, 2018). Multiple imputation was used to test the robustness of the PRO results in three studies (Lee et al, 2008;Gimsing et al, 2010;Waage et al, 2010).…”

A systematic review of health‐related quality of life in longitudinal studies of myeloma patients

“…23,39,59 After the literature search for this systematic review was completed, an additional analysis of the HRQoL data from the ASPIRE trial is published including these aspects. 60 Confidence intervals (95%) or standard deviations are reported in 15 of the 23 publications and the standard deviations ranged up to 34 on a 0-100 point scale. This clearly indicates that groups of patients in the treatment arms report very different scores, more than illustrated by the mean score.…”

A General Model for The Estimation of Societal Costs of Lost Production and Informal Care In Italy

“…Given this, instead of defining treatmentand subscale-specific levels of activity, we weighted all the "physical functioning" and "role functioning" scores reported in Stewart et al [33] in order to obtain a single multiple myeloma-specific level of ability (69.28).…”