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.

Trial registration: ClinicalTrials.gov NCT01080391.

Conflict of interest statement

Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

Figures

Fig 1.

CONSORT diagram.

Fig 2.

Adjusted least squares mean treatment difference in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module scores. Scores have been adjusted for baseline score, baseline score by visit interaction, and the random assignment stratification factors (baseline β2-microglobulin levels, prior bortezomib, and prior lenalidomide). For functioning scales, a positive difference is in favor of carfilzomib, lenalidomide, and dexamethasone (KRd). For symptom scales, a negative difference is in favor of KRd. Horizontal bars indicate 95% CIs. (*) Number of patients with data at that time point. (†) Presented in Stewart et al. GHS/QoL, Global Health Status/Quality of Life domain; KRd, carfilzomib, lenalidomide, and dexamethasone; Rd, lenalidomide and dexamethasone.

Fig 3.

Percentage of patient-reported outcome responders for European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) domain at cycles 3, 6, 12, and 18. A responder was defined as having a (A) ≥ 5-point improvement or (B) ≥ 15-point improvement from baseline for QLQ-C30 GHS/QoL. Missing data were assumed to have not reached the required improvement. GHS/QoL, Global Health Status/Quality of Life domain; KRd, carfilzomib, lenalidomide, and dexamethasone; Rd, lenalidomide and dexamethasone.

Fig 4.

Adjusted least squares mean change from baseline for the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and myeloma-specific module scores: (A) Global Health Status, (B) physical functioning, (C) role functioning, (D) fatigue, (E) nausea and vomiting, (F) pain, (G) adverse effects of treatment, and (H) disease symptoms. Scores have been adjusted for baseline score, baseline score by visit interaction, and the random assignment stratification factors (baseline β2-microglobulin levels, prior bortezomib, and prior lenalidomide). Differences between treatments are presented with 95% CIs at each visit. Longitudinal changes within treatment groups and level of significance are also indicated. Vertical bars indicate 95% CIs of the mean. (*) P < .05 change from baseline. KRd, carfilzomib, lenalidomide, and dexamethasone; Rd, lenalidomide and dexamethasone.

Fig 5.

Change from baseline Global Health Status/Quality of Life (GHS/QoL) domain for patients with a partial response or better. Positive change indicates improved GHS/QoL. (*) P < .05 between-group differences. KRd, carfilzomib, lenalidomide, and dexamethasone; Rd, lenalidomide and dexamethasone.

Fig A1.

Mean European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) domain scores over time, stratified by the time of last assessment. Pattern 1 shows mean scores at each visit for patients with a GHS/QoL score at all visits to cycle 18. Pattern 2 shows mean scores for patients with GHS/QoL scores up to cycle 12. Pattern 3 shows mean scores for patients with GHS/QoL scores up to cycle 6. Pattern 4 shows mean scores for patients with GHS/QoL scores up to cycle 3. Pattern 5 shows mean scores for patients with baseline GHS/QoL scores only. Graphs do not contain intermittent missing patterns. Percentages are based on the total number of patients in the carfilzomib, lenalidomide, and dexamethasone (KRd; n = 396) and lenalidomide and dexamethasone (Rd; n = 396) treatment groups.

Fig A2.

Cumulative distribution of change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 Global Health Status/Quality of Life domain scores. Positive change indicates improved health-related quality of life. KRd, carfilzomib, lenalidomide, and dexamethasone; Rd, lenalidomide and dexamethasone.