Phase II trial of combination therapy with bortezomib, pegylated liposomal doxorubicin, and dexamethasone in patients with newly diagnosed myeloma.
OBJECTIVE
This single-center, open-label, phase II trial evaluated the bortezomib, pegylated liposomal doxorubicin (PLD), and dexamethasone combination regimen (VDD) as initial treatment for patients with newly diagnosed multiple myeloma (MM).


METHODS
Enrolled patients (N = 40) received up to six 3-week cycles of treatment with bortezomib 1.3 mg/m(2) intravenously (IV) on days 1, 4, 8, and 11; PLD 30 mg/m(2) IV on day 4; and dexamethasone 20 to 40 mg daily as specified in the study design. The primary end point was the complete/near-complete response (CR/nCR) rate after six cycles. Secondary end points included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The impact of VDD on stem-cell mobilization and collection also was evaluated.


RESULTS
After six cycles, the ORR was 85.0% (CR/nCR, 37.5%; very good partial response [VGPR] or better, 57.5%). Patients who underwent stem-cell transplantation (SCT) after VDD (n = 30) experienced increased rates of VGPR or better (53.3% to 76.6% after SCT). Overall, 1-year PFS and OS rates were 92.5% and 97.5%, respectively. Those who achieved VGPR or better after treatment with VDD showed a significantly greater 1-year PFS versus those who achieved less than VGPR (100% v 82%, respectively; P = .03). Similar results were observed in patients who underwent SCT. Grades 3 or 4 hematologic toxicities occurred in < or = 10% of patients; grade 2 painful neuropathy occurred in 7.5%; and grade 3 palmar-plantar erythrodysesthesia occurred in 2.5%.


CONCLUSIONS
VDD is highly effective for initial treatment of MM followed by SCT in appropriate patients, and it has a reasonable safety profile. Achievement of VGPR or better with this initial therapy predicted longer PFS, regardless of the consolidation therapy given.
Jakubowiak
Andrzej J
AJ
Comprehensive Cancer Center, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI 48109-5936, USA. ajakubow@umich.edu
Kendall
Tara
T
Al-Zoubi
Ammar
A
Khaled
Yasser
Y
Mineishi
Shin
S
Ahmed
Asra
A
Campagnaro
Erica
E
Brozo
Christine
C
Braun
Thomas
T
Talpaz
Moshe
M
Kaminski
Mark S
MS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000628:therapy; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage; D033581:Stem Cell Transplantation; D016019:Survival Analysis
D001897:Boronic Acids; D011719:Pyrazines; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin