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 1.0mg/m2 (days 1, 4, 8, 11, every 21 day) with T added from cycle 2 at 50mg/day, with 50mg increments per 10 patient cohorts, to a maximum dose of 200mg. In the absence of DLT's, the same reiteration of T dose increases was applied with a higher dose of V = 1.3mg/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 = 1.3mg/m2 and T = 150mg. 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).
Original language | English |
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Pages (from-to) | 1419-1427 |
Number of pages | 9 |
Journal | Leukemia |
Volume | 22 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2008 |
Externally published | Yes |