Efficacy of proteasome inhibitor-based maintenance following autologous transplantation in multiple myeloma: A systematic review and meta-analysis

Eur J Haematol. 2021 Jan;106(1):40-48. doi: 10.1111/ejh.13506. Epub 2020 Oct 16.

Abstract

Introduction: Lenalidomide maintenance, commonly prescribed in the postautologous transplantation (AHCT) setting for multiple myeloma (MM), is associated with development of secondary primary malignancies (SPM). Proteasome inhibitor maintenance (PIM) has also been evaluated in MM. We conduct a systematic review/meta-analysis to assess the efficacy of PIM in MM.

Methods: Performing a comprehensive search of the medical literature using PubMed/Medline and EMBASE on September 11, 2019, we extracted data on clinical outcomes related to benefits (OS, PFS, and depth of hematologic response [DOHR]) and harms (SPM and adverse events). 2144 references were identified; three studies were eligible for inclusion.

Results: A total of 1760 patients were included in the analysis; 507 patients received bortezomib and 395 received ixazomib maintenance. Control arms were either placebo (n = 261) or thalidomide (n = 358). PIM did not improve OS (HR 0.88, 95% CI 0.73-1.05, P = .15) but improved PFS (HR 0.77, 95% CI 0.69-0.86, P ≤ .00001) and DOHR (HR 0.88, 95% CI 0.79-0.98, P = .02) compared with control. There were no significant differences between PIM and control regarding SPM (p = NS) and ≥grade 3 peripheral neuropathy (PN) (p = NS).

Conclusions: PIM following AHCT in MM improves PFS and DOHR without an increase in development of SPM or severe PN compared with placebo/thalidomide.

Keywords: autologous hematopoietic cell transplantation; maintenance therapy; multiple myeloma; proteasome inhibitors.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Combined Modality Therapy
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Maintenance Chemotherapy
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / mortality
  • Multiple Myeloma / therapy*
  • Prognosis
  • Proteasome Inhibitors / administration & dosage*
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Proteasome Inhibitors