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

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Expert Rev Hematol. 2021 Sep 23. doi: 10.1080/17474086.2021.1983427. Online ahead of print.

ABSTRACT

IntroductionMultiple 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 coveredThis 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 opinionIn the next 5 years, the results of ongoing research and trials are likely to focus on the therapeutic impact and treatment decisions associated with1q21+ in MM.

PMID:34551651 | DOI:10.1080/17474086.2021.1983427