"The importance of this study is that it clearly shows, with no increased toxicity, the combination of bortezomib and pegylated liposomla doxorubicin is effective in patients who have been heavily pretreated and in patients with anthracycline exposure."
Dr. Joan Bladé

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Joan Blade, Jesus San Miguel, Arnon Nagler, Pieter Sonneveld, Andrew Spencer, Tadeusz Robak, Kathleen Hennessey, Suneel D. Mundle, Sen H. Zhuang, Jean-Luc Harousseau, Robert Z. Orlowski Hospital Clinic i Provincial, Barcelona, Spain; Hematology Department, Hospital Clinico Universitario de Salamanca, Salamanca, Spain; Division of Hematology, Chaim Sheba Medical Center, Tel Hashomer, Israel; Erasmus MC, Rotterdam, Netherlands; Stem Cell Transplantation and Malignant Hematology Service, Alfred Hospital, Melbourne, Victoria, Australia; Medical University of Lodz, Lodz, Poland; Ortho Biotech Clinical Affairs, LLC, Strongsville, OH, USA; Ortho Biotech Clinical Affairs, LLC, Naperville, IL, USA; Johnson Johnson Pharmaceutical Research and Development, LLC, Raritan, NJ, USA; Hematology Department, University Hospital Hotel-Dieu, Nantes, France; University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Recently, a significant improvement in time to progression (TTP) was reported for pegylated liposomal doxorubicin (PLD) + bortezomib combination therapy vs. bortezomib monotherapy in a phase III randomized trial in relapsed or refractory multiple myeloma (RRMM) (Orlowski, JCO 2007). This pre-specified analysis assessed the efficacy of PLD+bortezomib in RRMM based on the number of prior lines of therapy and previous anthracycline exposure status. Patients with 1 prior therapy were randomized to receive PLD at 30 mg/m2 on day 4 and bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11, or bortezomib alone for up to eight 21-day cycles, or at least 2 cycles beyond CR, or optimal response unless disease progression, or unacceptable toxicities occurred. The baseline beta-2 microglobulin levels were comparable between the subgroup with 2 prior treatments and that with 1 treatment (median 3.98 vs. 4.01 mg/L), as well as between anthracycline-exposed and -nave patients (median 3.91 vs. 4.55 mg/L). The improved TTP reported previously with PLD+bortezomib over bortezomib in the total study population was similarly observed in all four subgroups of patients (patients with 2 lines of prior therapy or 1 prior therapy, anthracycline-exposed (median 144 mg/m2 in both treatment arms) or nave groups (Table)), indicating a consistent therapeutic benefit favoring the PLD+bortezomib combination. Furthermore, TTP was comparable for the PLD+bortezomib combination between groups with 2 lines of prior therapy vs. 1 prior therapy (heterogeneity test, p=0.523), as well as patients who were anthracycline-exposed or -nave (heterogeneity test, p=0.716). Incidence of treatment-related SAEs, grade 3/4 neuropathy, and symptomatic cardiac events was comparable between treatment arms in each subgroup (Table). PLD-related hand-foot syndrome was also <10% in all PLD+bortezomib subgroups. These results demonstrate that PLD+bortezomib combination therapy significantly improves TTP compared to bortezomib alone, regardless of the number of prior lines of therapy, or anthracycline exposure.

Abstract #410 appears in Blood, Volume 110, issue 11, November 16, 2007

Keywords: Doxil|Velcade|Randomized

Disclosure: Employment: K. Hennessey, S. Mundle, and S. Zhuang are employees of Johnson Johnson. Consultancy: J. Blade, Johnson Johnson; J. San Miguel, Johnson Johnson, Celgene, Pharmion; P. Sonneveld, Johnson Johnson. Ownership Interests:; K. Hennessey, S. Mundle, and S. Zhuang own stock in Johnson Johnson. Research Funding: J. Blade, Johnson Johnson; T. Robak, Johnson Johnson. Honoraria Information: J. Blade, Johnson Johnson; J. San Miguel, Johnson Johnson, Celgene, Pharmion; A. Spencer, Johnson Johnson; JL Harousseau, Millennium. Membership Information: J. San Miguel, Johnson Johnson, Celgene, Pharmion; A. Spencer, Johnson Johnson; JL Harousseau, Johnson Johnson; RZ Orlowski, Millennium and Johnson Johnson.

Monday, December 10, 2007 11:15 AM

Session Info: Simultaneous Session: Myeloma: Novel Therapies in Relapsed Multiple Myeloma (11:00 a.m.-12:30 p.m.)