Author(s): Barlogie B, Anaissie E, van Rhee F, Haessler J, Hollmig K,
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Abstract Total therapy 3 incorporated bortezomib into a melphalan-based tandem transplant regimen for 303 newly diagnosed patients with myeloma. Induction chemotherapy prior to and consolidation chemotherapy after transplants each consisted of two cycles of VTD-PACE (bortezomib, thalidomide, dexamethasone and 4-d continuous infusions of cis-platin, doxorubicin, cyclophosphamide, etoposide); 3-year maintenance comprised monthly cycles of VTD in the first and TD in the remaining years. The median age was 59 years (age >64 years, 28\%). A minimum of 20 x 10(6) CD34 cells/kg was collected in 87\% of patients; 83\% completed both transplants, and only 5\% suffered a treatment-related death. At 24 months, 83\% had achieved near-complete remission, which was sustained in 88\% at 2 years from its onset. With a median follow-up of 20 months, 2-year estimates of event-free and overall survival were 84\% and 86\% respectively. The 44 patients who experienced an event more often had a high-risk gene array profile, cytogenetic abnormalities and indicators of high lactate dehydrogenase, beta-2-microglobulin, creatinine and International Staging System stage. Toxicities of grade > 2 included thrombo-embolic events in 27\% and peripheral neuropathy in 12\%. Results of this phase-2 study demonstrated that bortezomib could be safely combined with multi-agent chemotherapy, effecting near-complete remission status and 2-year survival rates in more than 80\% of patients.
This article was published in Br J Haematol
and referenced in Translational Medicine