TY - JOUR
T1 - Phase II trial of combination therapy with bortezomib, pegylated liposomal doxorubicin, and dexamethasone in patients with newly diagnosed myeloma
AU - Jakubowiak, Andrzej J.
AU - Kendall, Tara
AU - Al-Zoubi, Ammar
AU - Khaled, Yasser
AU - Mineishi, Shin
AU - Ahmed, Asra
AU - Campagnaro, Erica
AU - Brozo, Christine
AU - Braun, Thomas
AU - Talpaz, Moshe
AU - Kaminski, Mark S.
PY - 2009/10/20
Y1 - 2009/10/20
N2 - Purpose: 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). Patients and Methods: Enrolled patients (N = 40) received up to six 3-week cycles of treatment with bortezomib 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11; PLD 30 mg/m2 IV on day 4; and dexamethasone 20 to 40 mg daily as specified in the study design. The primary end point was the complete/nearcomplete 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 ≤ 10% of patients; grade 2 painful neuropathy occurred in 7.5%; and grade 3 palmar-plantar erythrodysesthesia occurred in 2.5%. Conclusion: 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.
AB - Purpose: 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). Patients and Methods: Enrolled patients (N = 40) received up to six 3-week cycles of treatment with bortezomib 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11; PLD 30 mg/m2 IV on day 4; and dexamethasone 20 to 40 mg daily as specified in the study design. The primary end point was the complete/nearcomplete 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 ≤ 10% of patients; grade 2 painful neuropathy occurred in 7.5%; and grade 3 palmar-plantar erythrodysesthesia occurred in 2.5%. Conclusion: 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.
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U2 - 10.1200/JCO.2008.19.5370
DO - 10.1200/JCO.2008.19.5370
M3 - Article
C2 - 19738129
AN - SCOPUS:77649092410
SN - 0732-183X
VL - 27
SP - 5015
EP - 5022
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 30
ER -