Jingshan Zhang

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

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).

Factors that influence health-related quality of life in newly diagnosed patients with multiple myeloma aged ≥ 65 years treated with melphalan, prednisone and lenalidomide followed by lenalidomide maintenance: results of a randomized trial

Abstract In the MM-015 trial, melphalan–prednisone–lenalidomide followed by lenalidomide maintenance (MPR-R) significantly prolonged progression-free survival versus melphalan–prednisone (MP) in newly diagnosed patients with multiple myeloma aged ≥ 65 years. Health-related quality of life (HRQoL), a secondary endpoint of MM-015, was also improved with MPR-R. This sub-analysis evaluated the impact of individual predictive factors on HRQoL. Patients completed HRQoL questionnaires at baseline, every third cycle and at progressive disease (PD)/treatment discontinuation. In a mixed-effects model female gender, advanced age and PD negatively affected HRQoL while better treatment responses showed positive effects. Compared to PD, HRQoL during MPR-R treatment was statistically significantly better in two of six preselected domains both of which were also clinically meaningful. HRQoL scores at end of treatment were all either improved or not statistically significantly different versus baseline. In conclusion, continuous treatment with MPR-R, which delays PD, appears to be associated with clinically meaningful improvements in HRQoL.

Impact of maintenance therapy on subsequent treatment in patients with newly diagnosed multiple myeloma: use of “progression-free survival 2” as a clinical trial end-point

Maintenance therapy has generally been shown to improve outcomes in newly diagnosed multiple myeloma (NDMM).1–8 Increases in progression-free survival (PFS) and overall survival (OS) have been demonstrated in some trials of maintenance therapy,4–6 but others have reported improved PFS with no corresponding improvement in OS.1–3 The lack of OS benefit may be due to crossover and insufficient follow-up, as well as the fact that these trials were not powered to detect differences in OS between treatment groups. Theoretically, an experimental treatment may negatively affect OS (despite improving PFS) by increasing long-term toxicity or altering the tumor population or microenvironment to induce drug resistance or evolution of an aggressive clone.9–11 To account for these possibilities, the European Medicines Agency (EMA) has recently recommended using “progression-free survival 2” (PFS2) as a clinical end-point to evaluate the efficacy of maintenance therapy in hematology/oncology trials.10 To rule out possible negative effects of treatment on the efficacy of next-line therapy, PFS2 in the experimental arm should be sufficiently superior to that in the control arm.10 In this article, we explore the concept of PFS2 and apply it to a trial in NDMM patients to determine whether lenalidomide maintenance therapy influenced the efficacy of subsequent treatment.