title: Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group.
abstract: The International Myeloma Working Group consensus updates the definition for high-risk (HR) multiple myeloma based on cytogenetics Several cytogenetic abnormalities such as t(4;14), del(17/17p), t(14;16), t(14;20), nonhyperdiploidy, and gain(1q) were identified that confer poor prognosis. The prognosis of patients showing these abnormalities may vary with the choice of therapy. Treatment strategies have shown promise for HR cytogenetic diseases, such as proteasome inhibition in combination with lenalidomide/pomalidomide, double autologous stem cell transplant plus bortezomib, or combination of immunotherapy with lenalidomide or pomalidomide. Careful analysis of cytogenetic subgroups in trials comparing different treatments remains an important goal. Cross-trial comparisons may provide insight into the effect of new drugs in patients with cytogenetic abnormalities. However, to achieve this, consensus on definitions of analytical techniques, proportion of abnormal cells, and treatment regimens is needed. Based on data available today, bortezomib and carfilzomib treatment appear to improve complete response, progression-free survival, and overall survival in t(4;14) and del(17/17p), whereas lenalidomide may be associated with improved progression-free survival in t(4;14) and del(17/17p). Patients with multiple adverse cytogenetic abnormalities do not benefit from these agents. FISH data are implemented in the revised International Staging System for risk stratification.
authors.affiliation: Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands;
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.affiliation: Laboratory for Genomics in Myeloma, University Cancer Center of Toulouse, Toulouse, France;
authors.forename: Hervé
authors.initials: H
authors.lastname: Avet-Loiseau
authors.affiliation: Winship Cancer Institute, Emory University Medical School, Atlanta, GA;
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.affiliation: Levine Cancer Institute/Carolinas Healthcare System, Charlotte, NC;
authors.forename: Saad
authors.initials: S
authors.lastname: Usmani
authors.affiliation: John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ;
authors.forename: David
authors.initials: D
authors.lastname: Siegel
authors.affiliation: Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.affiliation: Division of Hematology, National University Cancer Institute, Singapore;
authors.forename: Wee-Joo
authors.initials: WJ
authors.lastname: Chng
authors.affiliation: Department of Hematology, University Hospital, Nantes, France;
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Department of Hematology, Purpan University Hospital, Toulouse, France;
authors.forename: Michel
authors.initials: M
authors.lastname: Attal
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Minneapolis, MN;
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kyle
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire de Liège, Liège, Belgium;
authors.forename: Jo
authors.initials: J
authors.lastname: Caers
authors.affiliation: Medical Clinic V, Section for Multiple Myeloma, University of Heidelberg, Heidelberg, Germany;
authors.forename: Jens
authors.initials: J
authors.lastname: Hillengass
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada, Pamplona, Spain;
authors.forename: Jesús
authors.initials: J
authors.lastname: San Miguel
authors.affiliation: Department of Hematology, Free University Medical Center Amsterdam, Amsterdam, The Netherlands;
authors.forename: Niels W C J
authors.initials: NW
authors.lastname: van de Donk
authors.affiliation: Medical Clinic 2, Universitätsklinik Würzburg, Würzburg, Germany;
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: University Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain;
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.affiliation: International Myeloma Foundation, North Hollywood, CA;
authors.forename: Brian G M
authors.initials: BG
authors.lastname: Durie
authors.affiliation: University Hospital Heidelberg and National Center for Tumor Diseases Heidelberg, Heidelberg, Germany;
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.affiliation: Department of Hematology, University Hospital of Salamanca, Salamanca, Spain;
authors.forename: María-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.affiliation: Myeloma Unit, University of Torino, Torino, Italy; and.
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.affiliation: Division of Cancer Medicine, Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX.
authors.forename: Robert
authors.initials: R
authors.lastname: Orlowski
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069286:Bortezomib; D002869:Chromosome Aberrations / Q000145:classification; D003131:Combined Modality Therapy; D003582:Cytogenetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000077269:Lenalidomide; D009101:Multiple Myeloma / Q000145:classification / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D012307:Risk Factors; D013792:Thalidomide / Q000031:analogs & derivatives; D014182:Transplantation, Autologous
chemical_list: D013792:Thalidomide; D000069286:Bortezomib; C467566:pomalidomide; D000077269:Lenalidomide