Comparing efficacy and survivals of initial treatments for elderly patients with newly diagnosed multiple myeloma: a network meta-analysis of randomized controlled trials

Abstract

Objective: The aim of this study was to evaluate the efficacy and clinical outcome of initial therapies for elderly patients with multiple myeloma (MM).

Methods: Randomized controlled trials (RCTs) were obtained through a comprehensive search. Response rate, progression-free survival (PFS) and overall survival (OS) were the interested outcome measures. Network meta-analysis (NMA) using graph theory methodology to construct an NMA model, and sensitivity analysis were performed.

Results: Nineteen RCTs containing 7,235 participants and 17 treatments were included in the NMA. As compared to the classic melphalan plus prednisone (MP) regimen, the majority of other initial regimens showed higher rates of complete response/near complete response, overall response rate (ORR) and better PFS as well as OS. These four outcomes favored the two lenalidomide plus dexamethasone regimens (continuous lenalidomide and 18 cycles of lenalidomide plus dexamethasone), especially continuous lenalidomide plus dexamethasone regimen, over the majority of other regimens including the two established standard treatments (MP plus thalidomide or bortezomib) for elderly patients with newly diagnosed MM.

Conclusion: Continuous lenalidomide plus dexamethasone ranked as the best regimen in terms of ORR and OS for the treatment of elderly patients with newly diagnosed MM.

Keywords: elderly patients; initial therapies; multiple myeloma; network meta-analysis; previously untreated.

Figure 1

Flow diagram showing the publication selection process. Abbreviation: RCTs, randomized controlled trials.

Figure 2

Network plot of initial treatments included in this network meta-analysis. Notes: Circles represent the intervention as a node in the network, lines represent direct comparisons using randomized controlled trials (RCTs) and the thickness of lines corresponds to the number of RCTs included in each comparison. Abbreviations: CPR, cyclophosphamide plus prednisone and lenalidomide; CTD, cyclophosphamide plus thalidomide and dexamethasone; Ld 9 cycles, lenalidomide plus dexamethasone for 9 cycles; Ld 18 cycles, lenalidomide plus dexamethasone for 18 cycles; Ld continuous, lenalidomide plus dexamethasone in 28-day cycles until disease progression; MEL100, reduced-intensity stem cell transplantation using melphalan 100 mg/m²; MP, melphalan plus prednisone; MPR, MP plus lenalidomide; MPR-R, MPR regimen followed by lenalidomide maintenance therapy until a relapse or disease progression occurred; MPT, MP plus thalidomide; MPT-T, MPT cycles received maintenance therapy with oral thalidomide until disease progression in four trials; RCTs, randomized controlled trials; TD, thalidomide plus dexamethasone; VD, bortezomib plus dexamethasone; VMP, bortezomib plus melphalan plus prednisone; VMPS, VMP plus siltuximab; VMPT-VT, VMP plus thalidomide that followed by maintenance with bortezomib and thalidomide; VTD, bortezomib plus TD.

Figure 3

Differences in CR/nCR, ORR, PFS and OS between Ld continuous or VD regimen versus other initial regimens. Notes: (A) Network analysis of CR/nCR, (B) network analysis of ORR, (C) subnetwork analysis of PFS, (D) network analysis of OS and (E) subnetwork analysis of PFS. Abbreviations: CI, confidence interval; CPR, cyclophosphamide plus prednisone and lenalidomide; CR/nCR, complete response/near complete response; CTD, cyclophosphamide plus thalidomide and dexamethasone; HR, hazard ratio; Ld 9 cycles, lenalidomide plus dexamethasone for 9 cycles; Ld 18 cycles, lenalidomide plus dexamethasone for 18 cycles; Ld continuous, lenalidomide plus dexamethasone in 28-day cycles until disease progression; MEL100, reduced-intensity stem cell transplantation using melphalan 100 mg/m²; MP, melphalan plus prednisone; MPR, MP plus lenalidomide; MPR-R, MPR regimen followed by lenalidomide maintenance therapy until a relapse or disease progression occurred; MPT, MP plus thalidomide; MPT-T, MPT cycles received maintenance therapy with oral thalidomide until disease progression in four trials; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; RR, relative risk; TD, thalidomide plus dexamethasone; VD, bortezomib plus dexamethasone; VMP, bortezomib plus melphalan plus prednisone; VMPS, VMP plus siltuximab; VMPT-VT, VMP plus thalidomide that followed by maintenance with bortezomib and thalidomide; VTD, bortezomib plus TD.