Influence of Overlapping Genetic Abnormalities on Treatment Outcomes of Multiple Myeloma

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Abstract

Numerous genetic abnormalities affect treatment outcomes in multiple myeloma. The role of coexistent trisomy or hyperdiploidy and high-risk cytogenetic abnormalities (CGAs) is not well defined. We assessed the influence of overlapping genetic abnormalities in patients who received frontline autologous stem cell transplantation. A total of 491 consecutive patients between January 2009 and January 2016 were identified. High-risk CGAs included del(17p), t(4;14), t(14;16), and gain 1q21 by fluorescence in situ hybridization and del(13) by conventional cytogenetics. Thirty-two percent had a trisomy, 27% had a high-risk CGA, and 11% had both. Among patients with any trisomy, 3-year progression-free survival (PFS) and overall survival (OS) were 60% and 90%, respectively, compared to 25% and 65%, respectively, for patients with any high-risk CGA. Patients with co-existent trisomy and high-risk CGAs had 3-year PFS and OS of 43% and 89%, respectively, whereas those with isolated high-risk CGAs without trisomy had 3-year PFS and OS of 13% and 49%, respectively. The PFS (hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.1 to 3.3; P =.02) and OS (HR, 4.5; 95% CI, 1.5 to 13; P =.006) were worse for high-risk CGAs without versus those with concurrent trisomies. Our findings suggest a protective impact of trisomies in patients with high-risk CGAs and a potential need for revised risk stratification assessments to account for overlapping genetic abnormalities.

Original languageEnglish (US)
Pages (from-to)243.e1-243.e6
JournalTransplantation and Cellular Therapy
Volume27
Issue number3
DOIs
StatePublished - Mar 2021

Keywords

  • High-risk genetics
  • Hyperdiploidy
  • Multiple myeloma
  • Transplantation
  • Trisomy

ASJC Scopus subject areas

  • Hematology
  • Transplantation
  • Immunology and Allergy
  • Cell Biology
  • Molecular Medicine
  • Medicine(all)

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