IgH translocation with undefined partners is associated with superior outcome in multiple myeloma patients

Eur J Haematol. 2020 Sep;105(3):326-334. doi: 10.1111/ejh.13440. Epub 2020 Jun 9.

Abstract

Background: In multiple myeloma (MM), impact of specific chromosomal translocations involving IgH (14q21 locus, including t(4;14), t(11;14), and t(14;16)) has been explored extensively. However, over 15% MM patients harboring IgH translocation with undefined partners have long been ignored.

Methods: A prospective non-randomized cohort study with a total of 715 newly-diagnosed MM cases was conducted, 13.6% of whom were t(14;undefined) positive. The whole cohort was divided into four groups: no IgH split (47.7%); t(14;undefined) (13.6%); t(11;14) (17.6%); and t(4;14) or t(14;16) group (21.1%).

Results: Median OS for the four groups was 84.2, not reached (NR), 58.7, and 44.2 months, respectively, with P values for t(14;undefined) vs no IgH split, t(11;14), and t(4;14)/t(14;16) groups of 0.197, 0.022, and 0.001, respectively. In bortezomib-based group, the survival advantage gained by t(14;undefined) group was much more significant compared to t(11;14) and t(4;14)/t(14;16) groups. Importantly, t(14;undefined) turned out to be an independent predictive factor for longer OS of MM patients in multivariate analysis, especially in the context of bortezomib treatment. Similar results were also observed in the PUMCH external validation cohort.

Conclusion: Collectively, our data confirmed and externally validated the favorable prognosis of the t(14;undefined) groups, especially in the era of novel agents.

Keywords: IgH translocation; cytogenetics; multiple myeloma; prognosis; unknown partner chromosomes.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Chromosomes, Human, Pair 11
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 16
  • Chromosomes, Human, Pair 4
  • Female
  • Gene Frequency
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / mortality*
  • Multiple Myeloma / therapy
  • Prognosis
  • Proportional Hazards Models
  • Translocation, Genetic*

Substances

  • Biomarkers, Tumor
  • Immunoglobulin Heavy Chains