1. ¹Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA
2. ²Cancer Research and Biostatistics, Seattle, WA USA

Correspondence: Dr B Barlogie, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA. E-mail: barlogiebart@uams.edu

Received 7 December 2007; Revised 18 March 2008; Accepted 20 March 2008; Published online 24 April 2008.

Abstract

Bortezomib (V) was combined with thalidomide (T) and dexamethasone (D) in a phase I/II trial to determine dose-limiting toxicities (DLT's) and clinical activity of the VTD regimen in 85 patients with advanced and refractory myeloma. The starting dose of V was 1.0 mg/m² (days 1, 4, 8, 11, every 21 day) with T added from cycle 2 at 50 mg/day, with 50 mg increments per 10 patient cohorts, to a maximum dose of 200 mg. In the absence of DLT's, the same reiteration of T dose increases was applied with a higher dose of V=1.3 mg/m². D was added with cycle 4 in the absence of partial response (PR). Ninety-two percent had prior autotransplants, 74% had prior T and 76% abnormal cytogenetics. MTD was reached at V=1.3 mg/m² and T=150 mg. Minor response (MR) was recorded in 79%, and 63% achieved PR including 22% who qualified for near-complete remission. At 4 years, 6% remain event-free and 23% alive. Both OS and EFS were significantly longer in the absence of prior T exposure and when at least MR status was attained. The MMSET/FGFR3 molecular subtype was prognostically favorable, a finding since reported for a VTD-incorporating tandem transplant trial (Total Therapy 3) for untreated patients with myeloma (BJH 2008).