title: An abnormal nonhyperdiploid karyotype is a significant adverse prognostic factor for multiple myeloma in the bortezomib era.
abstract: Multiple myeloma is clinically heterogeneous and risk stratification is vital for prognostication and informing treatment decisions. As bortezomib is able to overcome several high-risk features of myeloma, the validity of conventional risk-stratification and prognostication systems needs to be reevaluated. We study the survival data of 261 previously untreated myeloma patients managed at our institution, where bortezomib became available from 2004 for the treatment of relapse disease. Patient and disease characteristics, and survival data were evaluated overall, and with respect to bortezomib exposure. Overall, the international staging system (ISS), metaphase karyotyping and interphase fluorescence in situ hybridization (FISH) were discerning of survival outcomes, where the median for the entire cohort was 5.2 years. However, when stratified by bortezomib exposure, only metaphase karyotyping was still discriminating of long-term prognosis. The presence of an abnormal nonhyperdiploid karyotype overrides all other clinical and laboratory parameters in predicting for a worse outcome on multivariate analysis (median survival 2.6 years, P = 0.001), suggesting that bortezomib used at relapse is better able to overcome adverse risk related to high tumor burden (as measured by the ISS) than adverse cytogenetics on conventional karyotyping. Metaphase karyotyping provides additional prognostic information on tumor kinetics where the presence of a normal diploid karyotype in the absence of any high-risk FISH markers correlated with superior survival and could act as a surrogate for lower plasma cell proliferation.
authors: Department of Hematology, Singapore General Hospital, Outram Road, Singapore, Republic of Singapore. daryl.tan@sgh.com.sg
authors: Daryl
authors: D
authors: Tan
authors: Gerrard
authors: G
authors: Teoh
authors: L C
authors: LC
authors: Lau
authors: Alvin
authors: A
authors: Lim
authors: T H
authors: TH
authors: Lim
authors: K C
authors: KC
authors: Yap
authors: P
authors: P
authors: Premalatha
authors: Z T
authors: ZT
authors: Lao
authors: Nelson
authors: N
authors: Wee
authors: Christine
authors: C
authors: Choo
authors: H C
authors: HC
authors: Wee
authors: S
authors: S
authors: Su
authors: Y S
authors: YS
authors: Lee
authors: L H
authors: LH
authors: Lee
authors: William
authors: W
authors: Hwang
authors: Y T
authors: YT
authors: Goh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D007621:Karyotyping / Q000379:methods*; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D009367:Neoplasm Staging; D011379:Prognosis; D011719:Pyrazines / Q000627:therapeutic use*; D012189:Retrospective Studies; D016879:Salvage Therapy; D014178:Translocation, Genetic; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib