Since 2003, 204 patients (pts) younger than 66 yrs with untreated active MM were randomly assigned to receive a 4 month treatment with Dex/Thal (n=100) or with a VAD-like regimen (n=104). Then, all pts were intended to proceed to peripheral blood stem cell (PBSC) mobilization using cytoxan 4 g/m2 + G-CSF 5 μg/kg and to receive high dose therapy (HDT) with melphalan 200 mg/m2 and autologous PBSC support. Pts in the Dex/Thal arm received orally Thal for 3 mths at a fixed dose of 200 mg/d combined with Dex, 40 mg/d for 4 days every other wk for 2 mths and then monthly for 2 mths. Pts in the VAD arm received the same Dex regimen plus 3 courses of 4 days continuous infusions of Doxorubicin (9 mg/m2/d for 4 days) and Vincristine (0.4 mg/d for 4 days), 4 wk apart. Anticoagulation prophylaxis wasn’t systematically given.

Main characteristics of pts included in both arms were similar, including age (mean 55.1 yr in the Dex/Thal arm vs 56.4 yr in the VAD arm), MM stage (stage III 78% vs 85%), isotype (IgA: 21% vs 32%, p=.55), serumβ2m (mean 5.2 mg/L vs 3.9 mg/L, p=.24) serum creatinine (≤300 μmol/L in all pts) and albumin levels. Data were analyzed in an intent to treat basis. Primary objective was the achievement of at least a very good partial response (VGPR), defined as a decrease in serum and urine monoclonal immunoglobulin by 90% or greater.

In both arms, 91% of pts proceeded to PBSC mobilization, PBSC harvests were similarly successful and 83% of pts received HDT and autotransplant. Before PBSC collection, 24.7% and 7.3% of pts were in VGPR in the Dex/Thal arm and in the VAD arm, respectively (p=.0027). Before HDT, VGPR rate was 34.7% in the Dex/Thal arm as compared to 12.6% in the VAD arm (p=.002). At 6 mths post transplant, the benefit of Dex/Thal wasn’t further observed with VGPR rates of 44.4% in the Dex/Thal arm and 41.7% in the VAD arm (p=.87). Six pts died in the Thal/Dex arm (including 4 early deaths, within 4 mths post randomization) as compared to 9 pts in the VAD arm (including 3 early deaths).

Venous thrombosis or pulmonary embolism were recorded in 22.8% of pts in the Dex/Thal arm and in 7.5% in the VAD arm (p=.004). A symptomatic peripheral neuropathy was observed in 17.4 % and 12.9% of pts, respectively (p=.42). Otherwise, toxicity profile were similar in both groups. Before PBSC mobilization, mean duration of hospitalization, whatever the cause, was 8.3 days in the Dex/Thal arm as compared to 20 days in the VAD arm (p=.0001).

This randomized study confirms that oral Dex/Thal is an effective first line treatment for symptomatic MM, and supports its use as an induction regimen which could be preferred to infusional VAD in candidates for HDT.

Disclosures: Thalidomide was given by Laphal laboratories and the study was supported by grants from Amgen company and by the Clinical Research Department of the “CH de Caen”.

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