NFKB1 -94ins/delATTG polymorphism is a novel prognostic marker in first line-treated multiple myeloma

Br J Haematol. 2015 Mar;168(5):679-88. doi: 10.1111/bjh.13197. Epub 2014 Nov 3.

Abstract

Nuclear factor kappa B (NFKB) plays an important role in multiple myeloma (MM), and bortezomib affects this pathway. We retrospectively analysed the effect of the NFKB1 -94ins/delATTG polymorphism on the survival of 295 MM patients treated at a single centre. The median progression-free survival (PFS) was 790 (659-921) d in patients with NFKB1 homozygous insertion genotype (I/I, n = 99) and 624 (515-733) d in deletion-carriers (I/D&D/D, n = 196, P = 0·013). In multivariate analysis, I/I carriers showed a favourable PFS compared to I/D&D/D with a hazard ratio of 0·622 (0·457-0·847), P = 0·003, in addition to international staging system (ISS) score, fluorescence in situ hybridization (FISH) risk score, age and bortezomib treatment. I/I patients benefited more from bortezomib treatment [PFS 902 (703-1101) and 580 (343-817), P = 0·008] than I/D&D/D patients [PFS 659 (487-831) and 488 (323-653), P = 0·531]; in addition the beneficial effect of low ISS score was not observed in the I/D&D/D group [PFS 639 (454-824) and 650 (458-842), P = 0·226], while it was clear in I/I patients [PFS 1140 (803-1477) and 580 (408-752), P < 0·001]. We conclude that homozygous carriers of the insertion allele of the NFKB1 -94ins/delATTG polymorphism have a better prognosis and probably benefit more from bortezomib treatment than MM patients carrying the deletion allele.

Keywords: NFKB1; bortezomib; multiple myeloma; nuclear factor kappa B; polymorphism.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Antineoplastic Agents / administration & dosage*
  • Base Sequence*
  • Biomarkers, Tumor / genetics*
  • Boronic Acids / administration & dosage*
  • Bortezomib
  • Disease-Free Survival
  • Female
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / genetics
  • Multiple Myeloma* / mortality
  • NF-kappa B p50 Subunit / genetics*
  • Polymorphism, Genetic*
  • Pyrazines / administration & dosage*
  • Retrospective Studies
  • Sequence Deletion*
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Boronic Acids
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • Pyrazines
  • Bortezomib