Health-related quality of life results from the MRC Myeloma IX clinical trial

The Medical Research Council (MRC) Myeloma IX trial (ISRCTN68454111) was a multi-centered study in the United Kingdom that recruited multiple myeloma (MM) patients (pts), either eligible (intensive pathway) (1114 pts) or non-eligible (non-intensive pathway) (856 pts) to receive an autologous stem cell transplant (ASCT). Each group of pts was randomized to different treatment arms, including randomization for two different types of bisphosphonates. Post-treatment, pts were further randomized to receive maintenance treatment or to be monitored without further treatment. The trial was finalized in 2014 and the results showed significant improvements in overall survival, progression-free survival and response to treatment, which were all primary end-points of the study. Among the secondary outcomes of the study was evaluation of health-related quality of life (HR-QoL).

Kara-Louise Royle from the Clinical Trials Research Unit (CTRU), University of Leeds, Leeds, United Kingdom, and colleagues examined the effects of treatment in HR-QoL of pts enrolled in the MRC Myeloma IX trial. To evaluate HR-QoL, participants received two different questionnaires: the EORTC QLQ-C30 and the QLQ-MY24. The EORTC QLQ-C30 is a general questionnaire for cancer patients designed by the European Organization of Research and Treatment of Cancer (EORTC). The QLQ-MY24 questionnaire is specifically designed for MM pts. This is one of the few MM studies that includes HR-QoL results from a big number of participants.

Key Data:

• Questionnaires were collected from three main patient groups = group A: intensive treatment, n= 1061 pts; group B: non-intensive treatment, n= 758 pts; group C = maintenance treatment, n= 751 pts
• Group A = induction treatment with cyclophosphamide, thalidomide and dexamethasone (CTD) vs cyclophosphamide, vincristine, doxorubicin and dexamethasone (CVAD)
• Group B = CTD vs melphalan and prednisolone (MP)
• Group C = maintenance with thalidomide vs observation only
• Time points of questionnaire collection = at baseline; 3 months; 6 months; 12 months; long-term = 2 years; 3 years; 4 years; 5 years
• Questionnaire return rate = good; lower return rates at baseline (20% missing in both group A and B and 44% in group C)
• Total missing questionnaires = 63% group A; 71% group B; 48% group C
• Subscales of interest = Pain; Fatigue; Global Health Status/QoL; Physical Functioning
• Intensive pathway = Fatigue lower with CTD vs CVAD at 3 months: -4.02 (95% Confidence Interval [CI], -7.43, -0.61, P = 0.02) with persistent trend for benefit at 6 and 12 months; Physical Functioning higher with CTD vs CVAD at 12 months: 4.49 (95% CI, 0.22-8.76, P = 0.04)
• Non-intensive pathway = Pain lower with CTD vs MP at 3 months: -8.88 (95% CI, -13.58, -4.18, P = 0.0002) with a persistent trend for benefit at 6 and 12 months
• Maintenance pathway = Global Health Status/QoL lower with thalidomide maintenance vs observation only at 3 months: -3.39 (95% CI, -6.33, -0.45, P = 0.02) with a persistent trend for detriment at 6 and 12 months
• Intensive pathway long-term follow-up = short-term negative effect on both Fatigue and Physical Functioning that could be attributable to high-dose therapy and ASCT
• Non-intensive and maintenance treatment long-term follow-up = no temporal trends
• Bisphosphonate treatment = no differences in any subscale between treatments

Conclusions

This study examines the health-related quality of life (HR-QoL) results of participants of the MRC Myeloma IX trial. The results reveal that the only factor with likely clinical relevance was Pain at three months in the non-intensive pathway in favor of the CTD group. Overall, the clinical benefits of this trial did not worsen the participants’ HR-QoL. Future clinical trials could consider evaluation of more specific and simplified measures to ensure standardization of HR-QoL protocols to specific treatment agents.