title: Bortezomib- and thalidomide-induced peripheral neuropathy in multiple myeloma: clinical and molecular analyses of a phase 3 study.
abstract: A subanalysis of the GIMEMA-MMY-3006 trial was performed to characterize treatment-emergent peripheral neuropathy (PN) in patients randomized to thalidomide-dexamethasone (TD) or bortezomib-TD (VTD) before and after double autologous transplantation (ASCT) for multiple myeloma (MM). A total of 236 patients randomized to VTD and 238 to TD were stratified according to the emergence of grade ≥2 PN. Gene expression profiles (GEP) of CD138+ plasma cells were analyzed in 120 VTD-treated patients. The incidence of grade ≥2 PN was 35% in the VTD arm and 10% in the TD arm (P < 0.001). PN resolved in 88 and 95% of patients in VTD and TD groups, respectively. Rates of complete/near complete response, progression-free and overall survival were not adversely affected by emergence of grade ≥2 PN. Baseline characteristics were not risk factors for PN, while GEP analysis revealed the deregulated expression of genes implicated in cytoskeleton rearrangement, neurogenesis, and axonal guidance. In conclusion, in comparison with TD, incorporation of VTD into ASCT was associated with a higher incidence of PN which, however, was reversible in most of the patients and did not adversely affect their outcomes nor their ability to subsequently receive ASCT. GEP analysis suggests an interaction between myeloma genetic profiles and development of VTD-induced PN.
authors.affiliation: "Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine, Bologna University School of Medicine, Bologna, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Tacchetti
authors.forename: Carolina
authors.initials: C
authors.lastname: Terragna
authors.forename: Monica
authors.initials: M
authors.lastname: Galli
authors.forename: Elena
authors.initials: E
authors.lastname: Zamagni
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Petrucci
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pezzi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Montefusco
authors.forename: Marina
authors.initials: M
authors.lastname: Martello
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tosi
authors.forename: Luca
authors.initials: L
authors.lastname: Baldini
authors.forename: Jacopo
authors.initials: J
authors.lastname: Peccatori
authors.forename: Miriana
authors.initials: M
authors.lastname: Ruggieri
authors.forename: Lucia
authors.initials: L
authors.lastname: Pantani
authors.forename: Antonio
authors.initials: A
authors.lastname: Lazzaro
authors.forename: Francesca
authors.initials: F
authors.lastname: Elice
authors.forename: Serena
authors.initials: S
authors.lastname: Rocchi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gozzetti
authors.forename: Guido
authors.initials: G
authors.lastname: Cavaletti
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D001369:Axons / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects*; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D016903:Drug Monitoring; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D060787:Neoplasm Grading; D055495:Neurogenesis / Q000235:genetics; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects*; D016019:Survival Analysis; D053668:Syndecan-1 / Q000235:genetics / Q000378:metabolism; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects*; D014182:Transplantation, Autologous
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; C508241:SDC1 protein, human; D053668:Syndecan-1; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone