A randomized trial with melphalan and prednisone versus melphalan and prednisone plus thalidomide in newly diagnosed multiple myeloma patients not eligible for autologous stem cell transplant

Abstract

Several trials comparing the efficacy of standard melphalan and prednisone (MP) therapy with MP plus thalidomide (MPT) in elderly patients with multiple myeloma (MM) have been reported, with inconsistent results. The primary goal of our study was to evaluate the efficacy and toxicity of MP versus MPT in newly diagnosed patients with MM who were transplant-ineligible or over age 65. A total of 135 patients were enrolled. Either minimal response or better or partial response or better were more frequent with MPT treatment (p = 0.001). After a median follow-up of 30 months, median progression-free survival (PFS) and overall survival (OS) were 33 and 52 months for MPT versus 22 and 32 months for MP, respectively. The comparison showed a significant advantage for MPT versus MP in PFS (p = 0.02) and only a trend for OS (p = 0.07). Severe adverse events were observed more frequently with MPT. In conclusion, our results show an improved activity of MPT at a cost of increased toxicity. We believe that MPT can be considered one of the new standard of care for elderly or transplant-ineligible patients with MM.

A systematic literature review and network meta-analysis of treatments for patients with untreated multiple myeloma not eligible for stem cell transplantation

“…[5,[16][17][18]33,38,35] Although no NMA was conducted on safety outcomes, the proportion of patients discontinuing treatment due to AEs and the reported grade 3/4 AEs from the 11 studies included in the sensitivity analysis was overall higher in triplet combinations compared with doublets. [16][17][18] Similar results were observed in the FIRST trial, where 44% of patients randomized to MPT reported grade 3/4 neutropenia compared with 28% in the Rd until progression group [5]. Where reported, grade 3/4 neuropathic events were consistently higher in patients receiving triplet versus doublet regimens.…”

“…In this SLR, the evidence networks consisted of a limited number of studies relative to the number of treatments under consideration and nearly all connections in the networks consisted of single trials. Additionally, included studies comparing MPT versus MP, [16][17][18] showed no heterogeneity (I 2 ¼ 0%). Thus, a fixed effect model was considered the most appropriate analysis.…”

“…Of the 208 full text articles screened and selected for further review, 192 were excluded for the following reasons: 65 did not include a population of interest; 14 did not evaluate an intervention or comparator of interest; 24 did not report on outcomes of interest; 54 had an inappropriate study design; and 35 due to other reasons. The resulting number of RCTs included was 16 (15 presented in full publications, [5,[16][17][18][21][22][23][24][25][26][27][28][29][30][31][32][33] and one presented in a conference abstract [34]). Two additional publications were identified for inclusion through manual searches of conference abstracts, [21,29] for a total of 18 publications reporting on 17 trials.…”

“…Two additional publications were identified for inclusion through manual searches of conference abstracts, [21,29] for a total of 18 publications reporting on 17 trials. [5,[16][17][18][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] A further two publications were identified providing safety data not available in the principal publications. [35,36] Of note, Fayers et al was excluded due to study design (meta-analysis); however, this study provided HR data for Beksac et al and Waage et al that was not otherwise available.…”

“…[14] The primary analysis network was thus composed of five trials evaluating Rd, VMP, MP and MPT (Figure 1(B)). [5,[16][17][18]21,30,36] Comparisons were evaluated using Rd as the reference treatment. Baseline characteristics were well distributed across trials, in terms of patient age and disease severity (Table 2).…”