Continuous treatment improves survival of newly diagnosed multiple myeloma patients achieving complete response: Data from 5 phase III trials including young and elderly patients

Abstract

Introduction: Several studies demonstrated that continuous therapy (CT) prolonged progression-free survival (PFS); conflicting data exist about overall survival (OS) for patients eligible and ineligible for autologous stem cell transplantation (ASCT). CT in patients with a sensitive disease is a matter of debate. We conducted a pooled analysis to clarify the role of CT in patients with a complete response (CR). Methods: Newly diagnosed myeloma patients enrolled in 5 phase III trials were analysed. Three trials included ASCT eligible patients: RV-MM-209 [MPR vs Mel200, followed by lenalidomide vs no maintenance), RV-MM-EMN-441 (CRD vs Mel200, followed by lenalidomide vs lenalidomide-prednisone maintenance) and HOVON65/GMMG-HD4 (PAD vs VAD, followed by bortezomib or thalidomide maintenance). Two studies enrolled elderly patients: GIMEMA-MM0305 (VMPT-VT vs VMP) and EMN01 (MPR vs CPR vs Rd, followed by lenalidomide vs lenalidomide-prednisone maintenance). The primary objective was to evaluate the impact of maintenance on PFS and OS in CR patients. Univariate analyses of OS and PFS were performed. Response was treated as time-dependent variable in a landmark analysis (at 4 months). Results: 2792 patients were retrospectively analysed. 2330 patients received maintenance, 503 (21%) of them achieved a CR (378 eligible vs 125 ineligible for ASCT) before maintenance. After a median follow-up of 47 months, a significant 5-year OS (79% vs 59%; HR0.5, p<0.0001) and 5-year PFS (66% vs 20%; HR0.3, p<0.001) advantage was reported among CR patients who received maintenance in comparison with no maintenance. Subgroup analyses by age (<65 years [young] vs >=65 years [elderly]) and type of treatment (ASCT vs conventional chemotherapy [CC]) were conducted. The PFS benefit with maintenance was confirmed across all subgroups: ASCT patients (median, 86 vs 40 months; HR0.3 p<0.0001), young-CC (median, NR vs 21 months; HR0.2, p<0.0001) and elderly-CC (median, 52 vs 34 months; HR0.5, p=0.003). No OS differences within maintenance and no maintenance were observed in young-ASCT patients (HR1.3, p=0.8). AnOS advantage in the maintenance group was reported in young-CC patients (HR0.4, p=0.06) and in elderly-CC patients (HR0.5, p=0.02). Conclusion: Maintenance treatment prolongs PFS, regardless of age and type of treatment, in CR patients. An OS benefit with maintenance was reported among patients treated with CC. Maintenance is particularly beneficial in patients with sensitive disease.