The Impact of Lenalidomide, Bortezomib, and Dexamethasone Treatment on Health-Related Quality of Life in Transplant-Eligible Patients with Newly-Diagnosed Multiple Myeloma: Results from the IFM/DFCI 2009 Trial
Authors: Roussel Murielle , Hebraud Benjamin , Hulin Cyrille , Perrot Aurore , Caillot Denis , Macro Margaret , Arnulf Bertrand , Belhadj Karim , Garderet Laurent , Facon Thierry , Guo Shien , Altincatal Arman , Dhanasiri Sujith , Leleu Xavier , Moreau Philippe , Attal Michel 
Published: October 2019

Abstract

Introduction: Multiple myeloma is one of the most debilitating hematological diseases. Most patients (pts) present with pain, fatigue, and bone lesions, and have a significantly worse health-related quality of life (HRQoL) compared with the general population. The IFM/DFCI 2009 trial demonstrated the clinical benefits of lenalidomide, bortezomib, and dexamethasone (RVd) as induction and consolidation therapy with or without stem cell transplantation (SCT) in newly-diagnosed multiple myeloma (NDMM) pts (Attal M, et al Blood 2015;126:abstract 391). RVd therapy plus SCT was associated with significantly longer progression-free survival in NDMM pts, although this did not translate to an overall survival (OS) benefit. The trial showed that transplant at time of relapse was feasible and not associated with a negative impact on OS. We evaluated changes in HRQoL in these pts, particularly during treatment with RVd to understand the impact of RVd with or without SCT on HRQoL.
Methods: The IFM/DFCI 2009 trial was a phase 3, multicenter, randomized, open-label trial in adult pts (N = 700) with NDMM aged ≤ 65 years, and was conducted in France, Belgium, and Switzerland. Pts were randomized (1:1) to: RVd for three 3-week cycles as induction followed by 5 cycles as consolidation (RVd-alone); or RVd for three 3-week cycles as induction therapy followed by SCT and then RVd for consolidation (RVd-SCT). Both arms then received lenalidomide maintenance for 12 months. HRQoL was assessed using the EORTC QoL-Core Questionnaire, QLQ-C30, and the MM module QLQ-MY20. Key domains of interest were global QoL, physical functioning, role functioning, fatigue, and pain (QLQ-C30); and side effects of treatment and disease symptoms (QLQ-MY20). In both arms, assessments were performed on 9 occasions (including at baseline, during induction, consolidation, maintenance, end of treatment, and during follow-up visits). Mean QLQ-C30 scores from the general population (Scott NW, et al. EORTC QoL Group Publications: Brussels; 2008) were used as a benchmark to help interpret the study findings.
Results: Compliance rates with the QLQ-C30 were generally high at baseline for both treatment arms (RVd-SCT 88.6%; RVd-alone 90.3%), and remained high at the end of the induction period (RVd-SCT 72%; RVd-alone 76%). Statistically significant (P < 0.05) improvements in mean changes from baseline were observed at the end of induction therapy with RVd for both treatment arms in the QLQ-C30 domains of global QoL, physical functioning, role functioning, and pain (not fatigue); and in the QLQ-MY20 domains of disease symptoms except for side effects of treatment (Table). Pts in the RVd-SCT group experienced a significant (P < 0.001) and clinically meaningful short-term worsening in most domains following SCT, but scores gradually improved over time. All key domains of interest for QLQ-C30 that were impaired at the time of diagnosis versus the reference values for the general population (male 52%; age range 50-59 years), improved over time in both treatment arms at the end of induction therapy, and continued to improve during consolidation and maintenance periods. Furthermore, these improvements were maintained throughout the rest of the post-treatment follow-up period and were at a level that was close, or equivalent to those experienced by the general population at follow-up visit 2 (Figure).
Conclusions: Most functional and symptom domains of HRQoL that were impaired at the time of diagnosis significantly improved during treatment with RVd in SCT-eligible pts with NDMM. This improvement in HRQoL was further increased over the subsequent treatment phases to the level of HRQoL experienced by the general population. This study complements clinical data from the IFM/DFCI 2009 trial, which demonstrated that QoL outcomes for pts could be improved by combination therapy with lenalidomide and bortezomib, thus providing additional support for the use of RVd as induction and consolidation treatment for SCT-eligible pts with NDMM. Furthermore, RVd treatment post-induction seems to improve pt QoL (relative to baseline and measured just before SCT) and could potentially be a strategy to minimize the burden associated with SCT. Further research is warranted to help understand this impact.

Disclosures
Roussel: Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy. Hebraud:Amgen: Consultancy; Celgene: Consultancy, Other: Lecture fees, Research Funding; Janssen: Consultancy, Other: Lecture fees; travel and accommodation for congress, Research Funding; Takeda: Consultancy; Sanofi: Consultancy. Hulin:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Perrot:Celgene: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Sanofi: Honoraria. Macro:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress. Belhadj:Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Garderet:Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy. Facon:Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Guo:Celgene Corporation: Consultancy. Altincatal:Evidera: Consultancy, Employment. Dhanasiri:Celgene International: Employment, Equity Ownership. Leleu:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Moreau:Amgen: 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; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees.