Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma

Abstract

Purpose: The long-term impact of thalidomide plus dexamethasone (thal/dex) as primary therapy for newly diagnosed multiple myeloma (MM) is unknown. The goal of this study was to compare thalidomide plus dexamethasone versus placebo plus dexamethasone (placebo/dex)as primary therapy for newly diagnosed MM.

Patients and methods: In this double-blind, placebo-controlled trial, patients with untreated symptomatic MM were randomized to thal/dex (arm A) or to placebo plus dexamethasone (dex) (arm B). Patients in arm A received oral thalidomide 50 mg daily, escalated to 100 mg on day 15, and to 200 mg from day 1 of cycle 2 (28-day cycles). Oral dex 40 mg was administered on days 1 through 4, 9 through 12, and 17 through 20 during cycles 1 through 4 and on days 1 through 4 only from cycle 5 onwards. Patients in arm B received placebo and dex, administered as in arm A. The primary end point of the study was time to progression. This study is registered at http://ClinicalTrials.gov (NCT00057564).

Results: A total of 470 patients were enrolled (235 randomly assigned to thal/dex and 235 to placebo/dex). The overall response rate was significantly higher with thal/dex compared with placebo/dex (63% v 46%), P < .001. Time to progression (TTP) was significantly longer with thal/dex compared with placebo/dex (median, 22.6 v 6.5 months, P < .001). Grade 4 adverse events were more frequent with thal/dex than with placebo/dex (30.3% v 22.8%).

Conclusion: Thal/dex results in significantly higher response rates and significantly prolongs TTP compared with dexamethasone alone in patients with newly diagnosed MM.

Fig 1

Patient disposition.

Fig 2

(A) Time to progression of patients receiving thalidomide plus dexamethasone (yellow) versus placebo plus dexamethasone (blue). Time to progression was 22.6 months for thalidomide/dexamethasone median and 6.5 months for placebo/dexamethasone (P < .001; hazard ratio [HR] = 0.43; 95% CI, 0.32 to 0.58). (B) Progression-free survival (PFS) of patients receiving thalidomide/dexamethasone (yellow) versus placebo plus dexamethasone (blue). Median PFS was 14.9 months for thalidomide/dexamethasone and 6.5 months for placebo/dexamethasone (P < .001; HR = 0.50; 95% CI, 0.38 to 0.64).

Fig 3

Overall survival of patients receiving thalidomide and dexamethasone (yellow) versus placebo and dexamethasone (blue).