Relapsed and refractory multiple myeloma: A systematic review and network meta-analysis of the efficacy of novel therapies

Br J Haematol. 2023 Mar;200(6):694-703. doi: 10.1111/bjh.18654. Epub 2023 Jan 20.


The prognosis of multiple myeloma (MM) has dramatically improved with the development of new drugs, and it has become important to determine the appropriate combinations of these novel agents. This study was a systematic review and network meta-analysis (NMA) of randomized trials in patients with relapsed and/or refractory (RR) MM. The PubMed, Cochrane, and Embase databases were searched for randomized trials from 1 January 2002 to 28 February 2022 of patients treated for MM. The primary end-point was progression-free survival (PFS), evaluated as a hazard ratio (HR) with a 95% confidence interval (95% CI) compared to dexamethasone (DEX). The p-score was used to rank treatments. Of a total of 1136 abstracts screened, 37 studies were selected, including 34 treatment options for RRMM. Daratumumab, lenalidomide and DEX was found to be the best treatment for RRMM, with the best HR compared to DEX (HR, 0.13; 95% CI, 0.08-0.20; p-score 0.9796). There was no evidence of significant heterogeneity (I2 , 41.3%; p = 0.146). The current NMA confirmed the excellent efficacy of three-drug regimens including anti-CD38 antibodies to treat RRMM and provides background data to evaluate the efficacy of chimeric antigen receptor T-cell treatments and bispecific T-cell engager therapies.

Keywords: double-refractory myeloma; high risk myeloma; network meta-analysis; plasma cell malignancy.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Dexamethasone / therapeutic use
  • Humans
  • Lenalidomide / therapeutic use
  • Multiple Myeloma* / drug therapy
  • Network Meta-Analysis
  • Progression-Free Survival


  • Lenalidomide
  • Dexamethasone