The Clinical Impact and Molecular Biology of del(17p) in Multiple Myeloma Treated with Conventional or Thalidomide-Based Therapy

K.D. Boyd, F.M. Ross, W.J. Tapper, L. Chiecchio, G. Dagrada, Z.J. Konn, D. Gonzalez, B.A. Walker, S.L. Hockley, C.P. Wardell, W.M. Gregory, J.A. Child, G.H. Jackson, F.E. Davies, G.J. Morgan, NCRI Haematology Oncology Studies

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Abstract

Hemizygous deletion of 17p (del(17p)) has been identified as a variable associated with poor prognosis in myeloma, although its impact in the context of thalidomide therapy is not well described. The clinical outcome of 85 myeloma patients with del(17p) treated in a clinical trial incorporating both conventional and thalidomide-based induction therapies was examined. The clinical impact of deletion, low expression, and mutation of TP53 was also determined. Patients with del(17p) did not have inferior response rates compared to patients without del(17p), but, despite this, del(17p) was associated with impaired overall survival (OS) (median OS 26.6 vs. 48.5 months, P <0.001). Within the del(17p) group, thalidomide induction therapy was associated with improved response rates compared to conventional therapy, but there was no impact on OS. Thalidomide maintenance was associated with impaired OS, although our analysis suggests that this effect may have been due to confounding variables. A minimally deleted region on 17p13.1 involving 17 genes was identified, of which only TP53 and SAT2 were underexpressed. TP53 was mutated in <1% in patients without del(17p) and in 27% of patients with del(17p). The higher TP53 mutation rate in samples with del(17p) suggests a role for TP53 in these clinical outcomes. In conclusion, del(17p) defined a patient group associated with short survival in myeloma, and although thalidomide induction therapy was associated with improved response rates, it did not impact OS, suggesting that alternative therapeutic strategies are required for this group. (C) 2011 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)765-774
Number of pages10
JournalGenes, Chromosomes and Cancer
Volume50
Issue number10
DOIs
Publication statusPublished - Oct 2011

Keywords

  • CHRONIC LYMPHOCYTIC-LEUKEMIA
  • RANDOMIZED CONTROLLED-TRIAL
  • STEM-CELL TRANSPLANTATION
  • P53 GENE DELETION
  • LRF CLL4 TRIAL
  • PROGNOSTIC-FACTOR
  • TP53 MUTATION
  • SURVIVAL
  • DEXAMETHASONE
  • CLASSIFICATION

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    Boyd, K. D., Ross, F. M., Tapper, W. J., Chiecchio, L., Dagrada, G., Konn, Z. J., Gonzalez, D., Walker, B. A., Hockley, S. L., Wardell, C. P., Gregory, W. M., Child, J. A., Jackson, G. H., Davies, F. E., Morgan, G. J., & Studies, NCRI. H. O. (2011). The Clinical Impact and Molecular Biology of del(17p) in Multiple Myeloma Treated with Conventional or Thalidomide-Based Therapy. Genes, Chromosomes and Cancer, 50(10), 765-774. https://doi.org/10.1002/gcc.20899