Sustained Health-Related Quality of Life (HRQoL) Improvement in Newly Diagnosed Multiple Myeloma Patients Treated with Bortezomib/Melphalan/Prednisone Versus Melphalan/Prednisone: Results From the VISTA Trial.

The impact of multiple myeloma treatment on patient-reported health-related quality of life (HRQoL) merits careful evaluation since treatment effect and toxicity may impact HRQoL. Previously, the positive impact of achieving CR in the VISTA study on HRQoL had been reported at the fourth cycle after CR onset. The aim of this study was to describe the rate of patients who experienced a sustained HRQoL improvement after best response and the overall HRQoL impact of best response.

The VISTA trial was a randomized, open-label, multicenter study designed to compare the efficacy and safety of VMP to melphalan/prednisone (MP) in subjects with previously untreated multiple myeloma who were ineligible for transplantation. Patients were followed over a 9-cycle period (54 weeks) and for a post-treatment follow-up phase. Response to therapy was defined according to the European Group for Blood and Marrow Transplantation criteria. The European Organization for Research on Treatment of Cancer (EORTC) QLQ-C30, a HRQoL questionnaire commonly used in multiple myeloma, was administered at screening, day 1 of each cycle during the treatment phase, and every 8 weeks until progression during follow-up. A sustained HRQoL improvement was defined as a change in score of at least 5 points (Dubois et al, JCO 2006; 24:976–82) for at least 2 consecutive cycles after best response (Complete Response [CR], Partial Response [PR] or Minimal Response [MR]). The rate of sustained improvement and the time to sustained improvement were calculated in the population of patients who were followed for at least 2 cycles after best response (n=363). Treatment groups were compared using a log-rank test. Cox proportional hazard models were applied to explore the effect of covariates (type of best response, score at baseline, score at best response) on the chance of sustained improvement in each EORTC QLQ-C30 score.

Mean and median age of study patients was 72 and 71 years, respectively; 51% were female, mean and median KPS was 80. All EORTC domain scores were similar at baseline across the study arms. Worse health was reported in all domains with VMP arm at best tumor response onset. However, after best response onset, patients in the VMP arm had a higher sustained HRQoL improvement rate than those in the MP arm in 14 of the 15 EORTC QLQ-C30 scores. VMP patients had a slightly lower sustained response rate only in Cognitive Functioning: 27% vs 28%, respectively. VMP patients were more likely than MP patients to experience a statistically significant sustained response in three QLQ-C30 domains according to the log-rank test: Nausea/Vomiting (p=0.0095), Appetite Loss (p=0.0170), and Diarrhea (p=0.0082). The differences for Nausea and Diarrhea remained significant in the Cox models when adjusted for baseline score, score at best response, and type of response (CR, PR or MR). VMP patients also had a higher rate of sustained response over MP patients for Global Health (49% vs 40%), Pain (40% vs 32%), and Insomnia (32% vs 24%). However, these differences were not statistically significant.

Patients treated with VMP more frequently experienced a sustained HRQoL improvement in most of the EORTC QLQ-C30 domains than patients in the MP arm after best tumor response. In particular, the likelihood of a sustained improvement in Nausea and Diarrhea was significantly higher in VMP patients, independent of the type of response and the respective symptom score at baseline and at time of best response. Although the incidences of nausea and diarrhea were higher in the VMP arm at best response onset, these data suggest that HRQoL decrements reported by patients begin to improve with best response onset. Further analysis is planned.

Dhawan:Janssen Cilag: Employment, Equity Ownership. Robinson:Johnson & Johnson: Employment, Equity Ownership, Research Funding. Meunier:Mapi Values: Employment. Regnault:Mapi Values: Employment. Rosa:Mapi Values: Employment. Cakana:Janssen Cilag: Employment, Equity Ownership. van de Velde:Johnson & Johnson: Employment, Equity Ownership. Richardson:Millennium Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Keryx: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. San Miguel:Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; OrthoBiotech: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.