title: Prognostically significant cytotoxic T cell clones are stimulated after thalidomide therapy in patients with multiple myeloma.
abstract: The expanded T cell clones are associated with a prolonged survival in patients with multiple myeloma. We sought to confirm this prognostic significance in a multicenter patient cohort and investigate the effect of thalidomide on clones and T regulatory cells (T(regs)). Blood was collected from 120 patients enrolled in a Phase III trial of maintenance therapy +/- thalidomide after autologous stem cell transplantation. TCR Vbeta repertoire analysis identified T cell expansions in 48% of patients pre-transplant and 68% after 8-month maintenance. T cell expansions, previously shown to be clonal, were predominantly CD8+ (93%) and all 24 TCR Vbeta families tested were represented. Thalidomide therapy was associated with a significant increase in the incidence of patients with multiple expansions (49% vs. 23%; chi2 = 6.8; p = 0.01). The presence of expansions regardless of therapy was associated with a significantly longer median progression free survival (PFS) (32.1 vs. 17.6 months; chi2 = 5.6; p = 0.02) and overall survival (OS) (chi2 = 3.9; p < 0.05). Median PFS in the thalidomide arm was 50.9 months for patients with expansions and 28.3 months for patients without expansions (chi2 = 19.4; p = 0.0002). Thalidomide did not appear to modulate T(reg) numbers. Expanded T cell clones are prognostically significant and have an impact on progression after thalidomide therapy in a proportion of patients.
authors.affiliation: Institute of Haematology, Royal Prince Alfred Hospital, Sydney, Australia. ross.brown@sswahs.nsw.gov.au
authors.forename: Ross D
authors.initials: RD
authors.lastname: Brown
authors.forename: Andrew
authors.initials: A
authors.lastname: Spencer
authors.forename: Phoebe Joy
authors.initials: PJ
authors.lastname: Ho
authors.forename: Nola
authors.initials: N
authors.lastname: Kennedy
authors.forename: Karieshma
authors.initials: K
authors.lastname: Kabani
authors.forename: Shihong
authors.initials: S
authors.lastname: Yang
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Sze
authors.forename: Esther
authors.initials: E
authors.lastname: Aklilu
authors.forename: John
authors.initials: J
authors.lastname: Gibson
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Joshua
mesh_terms: D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003131:Combined Modality Therapy; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D018655:Lymphocyte Count; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D011379:Prognosis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013792:Thalidomide / Q000627:therapeutic use*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013792:Thalidomide