title: Randomized phase 2 trial of ixazomib and dexamethasone in relapsed multiple myeloma not refractory to bortezomib.
abstract: Proteasome inhibitors have become an integral part of myeloma therapy. Considerable efforts have gone into optimizing this therapeutic approach to obtain maximal proteasome inhibition with least toxicity. Ixazomib is the first oral proteasome inhibitor to enter the clinic and has been studied as a single agent as well as in various combinations. The current trial was designed to examine the efficacy and toxicity of combining 2 different doses of ixazomib (4 mg and 5.5 mg given weekly for 3 of 4 weeks) with 40 mg weekly of dexamethasone, in relapsed myeloma. Seventy patients were enrolled, 35 patients randomly assigned to each ixazomib dose. Overall, 30 (43%; 95% confidence interval, 31-55) of the patients achieved a confirmed partial response or better, with 31% achieving a response with 4 mg and 54% with 5.5 mg of ixazomib. The median event-free survival (EFS) for the entire study population was 8.4 months; 1-year overall survival was 96%. The EFS was 5.7 months for patients with prior bortezomib exposure and 11.0 months for bortezomib-naïve patients. A grade 3 or 4 adverse event considered at least possibly related to treatment was seen in 11 (32%) patients at 4 mg and in 21 (60%) at 5.5 mg. Dose reductions were more frequent with 5.5 mg dose. Overall, the ixazomib with dexamethasone has good efficacy in relapsed myeloma, is well-tolerated and with higher response rate at 5.5 mg, albeit with more toxicity. This study was registered at www.clinicaltrials.gov as #NCT01415882.
authors.affiliation: Division of Hematology and.
authors.forename: Shaji K
authors.identifier: 0000-0001-5392-9284
authors.initials: SK
authors.lastname: Kumar
authors.affiliation: Department of Biostatistics, Mayo Clinic. Rochester, MN.
authors.forename: Betsy R
authors.initials: BR
authors.lastname: LaPlant
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ; and.
authors.forename: Craig B
authors.initials: CB
authors.lastname: Reeder
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL.
authors.forename: Vivek
authors.initials: V
authors.lastname: Roy
authors.affiliation: Department of Biostatistics, Mayo Clinic. Rochester, MN.
authors.forename: Alese E
authors.initials: AE
authors.lastname: Halvorson
authors.affiliation: Division of Hematology and.
authors.forename: Francis
authors.initials: F
authors.lastname: Buadi
authors.affiliation: Division of Hematology and.
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ; and.
authors.forename: P Leif
authors.initials: PL
authors.lastname: Bergsagel
authors.affiliation: Division of Hematology and.
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.affiliation: Division of Hematology and.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Thompson
authors.affiliation: Division of Hematology and.
authors.forename: Jamie
authors.initials: J
authors.lastname: Crawley
authors.affiliation: Division of Hematology and.
authors.forename: Prashant
authors.initials: P
authors.lastname: Kapoor
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ; and.
authors.forename: Joseph
authors.initials: J
authors.lastname: Mikhael
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ; and.
authors.forename: Keith
authors.initials: K
authors.lastname: Stewart
authors.affiliation: Division of Hematology and.
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Hayman
authors.affiliation: Division of Hematology and.
authors.forename: Yi L
authors.initials: YL
authors.lastname: Hwa
authors.affiliation: Division of Hematology and.
authors.forename: Wilson
authors.initials: W
authors.lastname: Gonsalves
authors.affiliation: Division of Hematology and.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL.
authors.forename: Sikander
authors.initials: S
authors.lastname: Ailawadhi
authors.affiliation: Division of Hematology and.
authors.forename: David
authors.initials: D
authors.lastname: Dingli
authors.affiliation: Division of Hematology and.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Go
authors.affiliation: Division of Hematology and.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL.
authors.forename: Candido E
authors.initials: CE
authors.lastname: Rivera
authors.affiliation: Division of Hematology and.
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.affiliation: Division of Hematology and.
authors.forename: Martha Q
authors.initials: MQ
authors.lastname: Lacy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001896:Boron Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005998:Glycine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D001896:Boron Compounds; D000069286:Bortezomib; C548400:ixazomib; D003907:Dexamethasone; D005998:Glycine