Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma

被引:348
作者
Kumar, Shaji [1 ]
Flinn, Ian [2 ]
Richardson, Paul G. [3 ]
Hari, Parameswaran [4 ]
Callander, Natalie [5 ]
Noga, Stephen J. [6 ]
Stewart, A. Keith [7 ]
Turturro, Francesco [8 ]
Rifkin, Robert [9 ]
Wolf, Jeffrey [10 ]
Estevam, Jose [11 ]
Mulligan, George [11 ]
Shi, Hongliang [11 ]
Webb, Iain J. [11 ]
Rajkumar, S. Vincent [1 ]
机构
[1] Mayo Clin, Div Hematol, Rochester, MN 55905 USA
[2] Sarah Cannon Res Inst, Nashville, TN USA
[3] Dana Farber Canc Inst, Dept Med Oncol Hematol Malignancies, Boston, MA 02115 USA
[4] Med Coll Wisconsin, Div Hematol & Oncol, Milwaukee, WI 53226 USA
[5] Univ Wisconsin, Bone Marrow Hematol Clin, Ctr Comprehens Canc, Madison, WI USA
[6] Sinai Hosp, Baltimore, MD 21215 USA
[7] Mayo Clin Arizona, Div Hematol & Oncol, Scottsdale, AZ USA
[8] Louisiana State Univ, Dept Med, Feist Weiller Canc Ctr, Hlth Sci Ctr, Shreveport, LA 71105 USA
[9] Rocky Mt Canc Ctr, Denver, CO USA
[10] Univ Calif San Francisco, San Francisco, CA 94143 USA
[11] Millennium Pharmaceut Inc, Cambridge, MA USA
关键词
THALIDOMIDE PLUS DEXAMETHASONE; STEM-CELL TRANSPLANTATION; INDUCTION THERAPY; STRATIFICATION; PREDNISONE; MELPHALAN; SURVIVAL; EFFICACY; SAFETY; TRIAL;
D O I
10.1182/blood-2011-11-395749
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Combinations of bortezomib (V) and dexamethasone (D) with either lenalidomide (R) or cyclophosphamide (C) have shown significant efficacy. This randomized phase 2 trial evaluated VDC, VDR, and VDCR in previously untreated multiple myeloma (MM). Patients received V 1.3 mg/m(2) (days 1, 4, 8, 11) and D 40 mg (days 1, 8, 15), with either C 500 mg/m(2) (days 1, 8) and R 15 mg (days 1-14; VDCR), R 25 mg (days 1-14; VDR), C 500 mg/m(2) (days 1, 8; VDC) or C 500 mg/m(2) (days 1, 8, 15; VDC-mod) in 3-week cycles (maximum 8 cycles), followed by maintenance with V 1.3 mg/m(2) (days 1, 8, 15, 22) for four 6-week cycles (all arms) >= very good partial response was seen in 58%, 51%, 41%, and 53% (complete response rate of 25%, 24%, 22%, and 47%) of patients (VDCR, VDR, VCD, and VCD-mod, respectively); the corresponding 1-year progression-free survival was 86%, 83%, 93%, and 100%, respectively. Common adverse events included hematologic toxicities, peripheral neuropathy, fatigue, and gastrointestinal disturbances. All regimens were highly active and well tolerated in previously untreated MM, and, based on this trial, VDR and VCD-mod are preferred for clinical practice and further comparative testing. No substantial advantage was noted with VDCR over the 3-drug combinations. This trial is registered at www.clinicaltrials.gov (NCT00507442). (Blood. 2012;119(19):4375-4382)
引用
收藏
页码:4375 / 4382
页数:8
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