Originally published as JCO Early Release 10.1200/JCO.2008.19.5370 on September 8 2009

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Phase II Trial of Combination Therapy With Bortezomib, Pegylated Liposomal Doxorubicin, and Dexamethasone in Patients With Newly Diagnosed Myeloma

From the Comprehensive Cancer Center, Division of Hematology and Oncology; Blood and Marrow Transplant Program; and Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI.

Corresponding author: Andrzej J. Jakubowiak, MD, PhD, University of Michigan, 1500 E Medical Center Dr, Room 4216 Cancer Center, SPC 5936, Ann Arbor, MI 48109-5936; e-mail: ajakubow{at}umich.edu.

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/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 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.

Supported by Ortho Pharmaceuticals, Millennium Pharmaceuticals, and Johnson & Johnson Pharmaceutical Research & Development.

Presented at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA; the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL; the 11th International Myeloma Workshop, June 25-30, 2007, Kos, Greece; and the 49th Annual Meeting of the American Society of Hematology, December 8-11, 2007, Atlanta, GA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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