Lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance, improves health-related quality of life in newly diagnosed multiple myeloma patients aged 65 years or older: results of a randomized phase III trial

Abstract

The MM-015 trial assessed the effect of lenalidomide-based therapy on health-related quality of life. Patients (n=459) with newly diagnosed multiple myeloma aged 65 years or over were randomized 1:1:1 to nine 4-week cycles of lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance; or lenalidomide, melphalan, and prednisone, or melphalan and prednisone, with no maintenance therapy. Patients completed health-related quality of life questionnaires at baseline, after every third treatment cycle, and at treatment end. Health-related quality of life improved in all treatment groups during induction therapy. Patients receiving lenalidomide maintenance had the most pronounced improvements, Global Health Status/Quality of Life (P<0.05), Physical Functioning (P<0.01), and Side Effects of Treatment (P<0.05) out of 6 pre-selected health-related quality of life domains. More patients receiving lenalidomide maintenance achieved minimal important differences (P<0.05 for Physical Functioning). Therefore, lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance, improves health-related quality of life in patients with newly diagnosed multiple myeloma. (Clinicaltrials.gov identifier NCT00405756). ABSTRACTLenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance, improves health-related quality of life in newly diagnosed multiple myeloma patients aged 65 years or older:

Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide

“…Furthermore, during the MM-015 phase III trial, with a median follow up of 30 months, more patients treated with MPR-R achieved minimal important improvements in HRQoL outcomes compared with those on MP, and there were no significant differences in HRQoL outcomes between patients on continuous treatment versus placebo. 39,43 Although not all the statistically significant changes reached the MID threshold, Rd showed evidence of clinically meaningful improvement in Pain and in HRQoL as measured by EQ-5D, whereas MPT failed to demonstrate a clinically meaningful improvement in any domain (with the exception of 1 time point in EQ-5D). Neither treatment showed a clinically significant worsening of HRQoL in any domain.…”

“…42 The observed differences in HRQoL between continuous Rd and MPT likely reflect both the good tolerability of the Rd regimen (leading to fewer side effects of treatment) and prolonged time to progression with continuous Rd. Improvements in HRQoL have previously been reported during treatment with melphalan, prednisone, lenalidomide followed by lenalidomide maintenance (MPR-R) in patients with NDMM, 39,43 and the addition of thalidomide to MP did not negatively affect HRQoL. 44 However, our results contrast with the HRQoL trade-off reported with bortezomib in the VISTA trial, which compared MPV versus MP in NDMM patients and in which MPV had superior PFS and OS efficacy, but where patients' HRQoL was significantly compromised, especially in the first four cycles of treatment.…”

“…MM-specific MIDs were applied to the QLQ-C30 and QLQ-MY20 domains: Global Health Status (MID=7); Physical Functioning (MID=9); Pain (MID=12); Fatigue (MID=10); Disease Symptoms (MID=10); and Side Effects of Treatment (MID=6). 30,39,40 The Walters and Brazier 41 MID of 0.07 was applied to the EQ-5D utility. Rigorous MID methods, in which the mean and 95% confidence intervals (CI) of change must meet the MID, were applied and are reported where relevant.…”

Patient reported outcomes to support drug development decision making

“…The majority of PRO data that is captured does not make it onto the regulatory approved label, this is particularly noted in oncology [4] which is currently being actively addressed by industry and regulators [5]. PRO data, particularly HRQL data, provides essential contextualizing information in oncology so that the quality of improved survival can be understood from patient's perspective [6,7]. PROs also provide important supporting evidence of treatment benefit that are of value to other stakeholders.…”

Lenalidomide in the treatment of plasma cell dyscrasia: state of the art and perspectives

“…[8][9][10][11] In the current issue of the Journal, three interesting papers have been published evaluating the role of lenalidomide alone or in combination with steroids and alkylating agents in three different settings of patients with plasma cell dyscrasia. [12][13][14] Coman et al presented the results of a retrospective multicenter study on MM patients receiving lenalidomide alone or in combination with dexamethasone as salvage therapy after allo-SCT. 12 This study is the largest reported in this setting.…”