Health-Related Quality of Life in Transplant Ineligible Newly Diagnosed Multiple Myeloma Patients Treated with Either Thalidomide or Lenalidomide-Based Regimen Until Progression (HOVON-87/NMSG18 Study): A Prospective, Open-Label, Multicenter, Randomized, Phase 3 Study

Background: The overall survival of patients with Multiple Myeloma has improved due to effective, often continuous, therapy. However, knowledge on the impact of long term treatment on health-related quality of life (HRQoL) is limited. Methods: The HOVON87/NMSG18 study was a prospective, randomized, phase 3 study of newly diagnosed transplant ineligible multiple myeloma patients, comparing melphalan-prednisolone in combination with thalidomide or lenalidomide, followed by thalidomide or lenalidomide maintenance therapy (MPT-T or MPR-R). The EORTC QLQ-C30 and MY20 questionnaires were completed by patients at baseline, after 3 and 9 induction cycles and after 6 and 12 months of maintenance therapy. Linear mixed models and minimal important differences were used for between and within treatment arm HRQoL evaluation. Findings: 596 of 637 eligible patients participated in HRQoL reporting. Patients in both arms reported clinical relevant improvement in global QoL, future perspective, role and emotional functioning and the summary score, and less fatigue and pain, in general occurring after 6 to 12 months of maintenance only and independent of WHO performance at baseline. MPR-R treated patients reported clinically relevant worsening of diarrhoea and MPT-T treated patients reported a higher incidence of neuropathy. Patients who remained on lenalidomide maintenance therapy for at least 3 months reported clinically meaningful improvement in global QoL, role functioning and the summary score over time, without any clinical meaningful deteriorations. In contrast, patients on thalidomide reported clinically relevant worsening of peripheral neuropathy.   Interpretation: Treatment with both thalidomide- and lenalidomide-based regimens improved HRQoL, in general reaching clinical relevance during maintenance therapy only. Clinical relevant diarrhea was reported by lenaldiomide-treated and clinical relevant PNP by thalidomide-treated patients.   Trial Registration Number: The study was registered at www.trialregister.nl NTR1630. Funding Statement: Dutch Cancer Society KWF VU-2008 4246, Celgene Declaration of Interests: AW reports that the study was supported by Celgene and receives honoraria Takeda and grant from Amgen. MH reports compensation for work related to the study from NTNU Department of Cancer Research and Molecular Medicine and receives grant from Celgene Aps. MS receives personal fees from Celgene, Amgen, Janssen and Takeda. SZ receives research funding from Celgene, Janssen, Takeda and Amgen and serves on advisory board for Celgene, Janssen, Takeda and Amgen. LKN has received grants from Celgene, Janssen, Amgen and Takeda, during the conduct of the study. NA receives research funding from Celgene, Janssen, Takeda and Amgen. PS receives grants from Takeda, Karyopharma, and grants and personal fees from Celgene, Janssen-Cilag. M-DL has received personal fees from Celgene. U-HM has received lecture honoraria from Amgen, Takeda, Janssen, Mundipharma, Oncopeptides and serves on advisory board for Amgen. NvdD receives grants from Celgene, Janssen pharmaceuticals, Novatis, Amgen and BMS and serves at the advisory board for Celgene, Janssen pharmaceuticals, Novartis, Amgen, Takeda, BMS, Bayer, Servier. All other authors declare no conflicting interest. Ethics Approval Statement: The study protocol was approved by the Ethics Committee and conducted in accordance with the ethical principles of the Declaration of Helsinki and the Good Clinical Practice Guidelines. The authors obtained written informed consent from all participants.