title: Thalidomide consolidation improves progression-free survival in myeloma with normal but not up-regulated expression of fibroblast growth factor receptor 3: analysis from the Australasian Leukaemia and Lymphoma Group MM6 clinical trial.
abstract: The translocation t(4;14) is associated with a poor prognosis in myeloma, but its effect in the setting of new drugs such as thalidomide, bortezomib and lenalidomide continues to be investigated, and the role of candidate genes such as FGFR3 (fibroblast growth factor receptor 3) is not yet clarified. In the Australasian Leukaemia and Lymphoma Group (ALLG) MM6 randomized study comparing consolidation thalidomide and prednisolone with prednisolone alone following autologous stem cell transplant, patients on consolidation thalidomide and prednisolone had superior progression-free (PFS) and overall survival (OS). We now show that thalidomide consolidation benefited both t(4;14)-positive (PFS 29 vs. 17 months, p =0.03) and -negative (52 vs. 24 months, p =0.04) disease. PFS for patients with normal FGFR3 expression was significantly better than for those with up-regulated FGFR3 (31 vs. 21 months, p =0.02). Consolidation thalidomide conferred an improved PFS in patients with normal FGFR3 expression (41 vs. 19 months, p =0.02), but there was no improvement in patients with up-regulated FGFR3 (31 vs. 29 months, p =0.76). We conclude that consolidation thalidomide may mitigate the poor prognostic effect of t(4;14), and improves PFS in normal but not up-regulated FGFR3 expression. Thus the level of FGFR3 expression provides additional prognostic information to t(4;14) in myeloma induction and consolidation therapy.
authors.affiliation: Institute of Haematology, Royal Prince Alfred Hospital, Sydney, Australia. joy.ho@sswahs.nsw.gov.au
authors.forename: P Joy
authors.initials: PJ
authors.lastname: Ho
authors.forename: Ross D
authors.initials: RD
authors.lastname: Brown
authors.forename: Andrew
authors.initials: A
authors.lastname: Spencer
authors.forename: Melinda
authors.initials: M
authors.lastname: Jeffels
authors.forename: Daniel
authors.initials: D
authors.lastname: Daniher
authors.forename: John
authors.initials: J
authors.lastname: Gibson
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Joshua
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics* / Q000628:therapy; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D011379:Prognosis; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D033581:Stem Cell Transplantation / Q000379:methods; D013792:Thalidomide / Q000008:administration & dosage; D014178:Translocation, Genetic; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013792:Thalidomide; D011239:Prednisolone; D051498:Receptor, Fibroblast Growth Factor, Type 3