Current developments in the combination therapy of relapsed/refractory multiple myeloma

Expert Rev Anticancer Ther. 2020 Dec;20(12):1021-1035. doi: 10.1080/14737140.2020.1828071. Epub 2020 Oct 7.

Abstract

Introduction: Therapy for patients with multiple myeloma has improved dramatically over the past decade following the introduction of novel agents and combinations across the disease spectrum. When relapse or refractory disease develops, non-cross-resistant drugs, most often used in multidrug regimens, have provided significant improvements in patient outcomes. Despite these advances, myeloma remains incurable and additional therapeutic approaches, based on emerging molecular and cellular biology, are moving rapidly through development phases. Approaches new to myeloma, including antibody-drug conjugates, T-cell-directed therapies, and novel small molecules, are poised to bring in the next wave of treatment.

Areas covered: This review addresses recent data for the management of relapsed/refractory disease, rationale for agent and regimen selection and combinations, and options showing early promise in trials. Literature and abstracts pertaining to trial data published or presented up to 2019 are included.

Expert opinion: Therapeutic strategies continue to evolve in myeloma, with the application of existing platforms (e.g., antibody-drug conjugates) to target relevant biology (e.g., B cell maturation antigen). Within the next year, there will be additional agents approved for those with advanced disease, and combinations as well as placement in sequencing will deepen responses and improve outcomes for patients.

Keywords: Antibody–drug conjugates; BCMA; CAR T cell; CD38; MCL-1; XPO1; belantamab mafodotin; iberdomide; monoclonal antibody; small molecule.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Drug Development
  • Humans
  • Immunoconjugates / administration & dosage
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Recurrence

Substances

  • Antineoplastic Agents
  • Immunoconjugates