Network meta-analysis of efficacy of ixazomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma

Hematology. 2023 Dec;28(1):2156731. doi: 10.1080/16078454.2022.2156731.

Abstract

Objectives: In the absence of head-to-head comparisons across relapsed/refractory multiple myeloma (RRMM) treatments following the approval of the oral proteasome inhibitor ixazomib, in combination with lenalidomide and dexamethasone (IRd), we conducted an indirect comparison of the efficacy of IRd relative to several RRMM therapies using Bayesian fixed-effects network meta-analysis (NMA) models.

Methods: Data for the NMA were obtained through a systematic literature review (conducted in June 2020), which identified randomized controlled trials (base case) and observational studies (extended network analysis) reporting overall survival (OS), progression-free survival (PFS), and overall response rate (ORR).

Results: In the base case, IRd was associated with a significantly longer PFS than lenalidomide and dexamethasone (Rd), bortezomib monotherapy (V), dexamethasone (Dex), and pomalidomide and dexamethasone (Pom-dex), a significantly shorter PFS than daratumumab, lenalidomide, and dexamethasone (DRd), and a PFS comparable to elotuzumab, lenalidomide, and dexamethasone (ERd) and carfilzomib, lenalidomide, and dexamethasone (KRd). IRd was associated with a significantly longer OS than V, Dex, and Pom-dex, and an OS comparable to Rd, ERd, KRd, and DRd. The ORR of IRd was significantly higher than Rd, V, and Dex, significantly lower than KRd and DRd, and comparable to Pom-dex and ERd. The extended network analyses and sensitivity analyses were consistent with the base case.

Discussion: This NMA shows that IRd is relatively efficacious among RRMM treatments. Being an oral regimen, IRd is also convenient to manage.

Conclusion: IRd could be a preferable treatment option for many patients with RRMM, particularly those seeking an efficacious and convenient therapeutic option.

Keywords: Network meta-analysis; dexamethasone; efficacy; ixazomib; lenalidomide; relapsed/refractory multiple myeloma; systematic literature review.

Publication types

  • Meta-Analysis

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bayes Theorem
  • Dexamethasone / therapeutic use
  • Humans
  • Lenalidomide / therapeutic use
  • Multiple Myeloma* / drug therapy
  • Network Meta-Analysis
  • Observational Studies as Topic
  • Randomized Controlled Trials as Topic
  • Systematic Reviews as Topic

Substances

  • Dexamethasone
  • ixazomib
  • Lenalidomide