Phase II trial of combination therapy with bortezomib, pegylated liposomal doxorubicin, and dexamethasone in patients with newly diagnosed myeloma

Andrzej J. Jakubowiak, Tara Kendall, Ammar Al-Zoubi, Yasser Khaled, Shin Mineishi, Asra Ahmed, Erica Campagnaro, Christine Brozo, Thomas Braun, Moshe Talpaz, Mark S. Kaminski

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)5015-5022
Number of pages8
JournalJournal of Clinical Oncology
Volume27
Issue number30
DOIs
StatePublished - Oct 20 2009

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Dexamethasone
Stem Cell Transplantation
Disease-Free Survival
Multiple Myeloma
Therapeutics
Hematopoietic Stem Cell Mobilization
liposomal doxorubicin
Bortezomib
Survival Rate
Safety
Survival

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Jakubowiak, Andrzej J. ; Kendall, Tara ; Al-Zoubi, Ammar ; Khaled, Yasser ; Mineishi, Shin ; Ahmed, Asra ; Campagnaro, Erica ; Brozo, Christine ; Braun, Thomas ; Talpaz, Moshe ; Kaminski, Mark S. / Phase II trial of combination therapy with bortezomib, pegylated liposomal doxorubicin, and dexamethasone in patients with newly diagnosed myeloma. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 30. pp. 5015-5022.
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title = "Phase II trial of combination therapy with bortezomib, pegylated liposomal doxorubicin, and dexamethasone in patients with newly diagnosed myeloma",
abstract = "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.",
author = "Jakubowiak, {Andrzej J.} and Tara Kendall and Ammar Al-Zoubi and Yasser Khaled and Shin Mineishi and Asra Ahmed and Erica Campagnaro and Christine Brozo and Thomas Braun and Moshe Talpaz and Kaminski, {Mark S.}",
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Jakubowiak, AJ, Kendall, T, Al-Zoubi, A, Khaled, Y, Mineishi, S, Ahmed, A, Campagnaro, E, Brozo, C, Braun, T, Talpaz, M & Kaminski, MS 2009, 'Phase II trial of combination therapy with bortezomib, pegylated liposomal doxorubicin, and dexamethasone in patients with newly diagnosed myeloma', Journal of Clinical Oncology, vol. 27, no. 30, pp. 5015-5022. https://doi.org/10.1200/JCO.2008.19.5370

Phase II trial of combination therapy with bortezomib, pegylated liposomal doxorubicin, and dexamethasone in patients with newly diagnosed myeloma. / Jakubowiak, Andrzej J.; Kendall, Tara; Al-Zoubi, Ammar; Khaled, Yasser; Mineishi, Shin; Ahmed, Asra; Campagnaro, Erica; Brozo, Christine; Braun, Thomas; Talpaz, Moshe; Kaminski, Mark S.

In: Journal of Clinical Oncology, Vol. 27, No. 30, 20.10.2009, p. 5015-5022.

Research output: Contribution to journalArticle

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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