Chromosomal 1q21 abnormalities in multiple myeloma: a review of translational, clinical research, and therapeutic strategies

Expert Rev Hematol. 2021 Dec;14(12):1099-1114. doi: 10.1080/17474086.2021.1983427. Epub 2021 Oct 8.

Abstract

Multiple myeloma (MM) remains an incurable disease with a median overall survival of approximately 5 years. Gain or amplification of 1q21 (1q21+) occurs in around 40% of patients with MM and generally portends a poor prognosis. Patients with MM who harbor 1q21+ are at increased risk of drug resistance, disease progression, and death. New pharmacotherapies with novel modes of action are required to overcome the negative prognostic impact of 1q21+. Areas covered: This review discusses the detection, biology, prognosis, and therapeutic targeting of 1q21+ in newly diagnosed and relapsed MM. Patients with MM and 1q21+ tend to present with higher tumor burden, greater end-organ damage, and more co-occurring high-risk cytogenetic abnormalities than patients without 1q21+. The chromosomal rearrangements associated with 1q21+ result in dysregulation of genes involved in oncogenesis. Identification and characterization of the 1q21+ molecular targets are needed to inform on prognosis and treatment strategy. Clinical trial data are emerging that addition of isatuximab to combination therapies may improve outcomes in patients with 1q21+ MM. Expert opinion: In the next 5 years, the results of ongoing research and trials are likely to focus on the therapeutic impact and treatment decisions associated with 1q21+ in MM.

Keywords: 1q21; chromosome aberrations; cytogenetic analysis; multiple myeloma; prognosis; treatment outcome.

Publication types

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

MeSH terms

  • Chromosome Aberrations
  • Humans
  • Multiple Myeloma* / diagnosis
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / etiology
  • Prognosis