The “Bologna 2002” study was a phase 2 multicenter trial with thalidomide-dexamethasone (thal-dex) and double transplantation (Tx) of autologous peripheral blood stem cells (PBSCs) to support 2 sequential courses of high-dose melphalan (MEL) as up-front therapy for newly diagnosed patients with symptomatic multiple myeloma (MM). By study design, thal (200 mg/d) and pulsed dex (40 mg/d for 4 days, repeated monthly) were administered as primary remission induction therapy and were subsequently continued throughout the other treatment phases. An analysis was performed on the first 100 patients who were enrolled into the study. For comparison of their outcome, an equal number of pair mates were retrospectively selected among patients who entered the “Bologna 96” trial and received VAD as primary remission induction therapy followed by either single or double Tx. Case-matching was performed with respect to age (±2 years), serum β2-microglobulin (±1 mg/L) and clinical stage. The 2 groups of patients were also comparable with respect to the planned doses of cyclophosphamide (CTX, 7 g/m2) administered for PBSC collection and of MEL (200 mg/m2) given in preparation for first Tx. Aim of the present analysis was to evaluate whether administration of thal-dex (thal-positive group, “Bologna 2002” study) following CTX and first MEL increased the rate of response in comparison with the same treatments administered without added thal-dex (thal-negative group, “Bologna 96” study). Primary endpoint was the rate of complete remission (CR) + very good partial remission (VGPR), as calculated on an intent-to-treat basis at 30 days after CTX and at 90 days after first MEL (e.g. at which time thal-dex was discontinued). In the thal-positive group, the probability to attain ≥ VGPR increased from 21% after primary remission induction therapy to 38% after CTX and 63% after first MEL. The corresponding figures in the thal-negative group were 14%, 18% and 27%, respectively. Differences between the 2 groups in terms of ≥ VGPR rates after CTX and first MEL were statistically significant in favor of the thal-positive group (P=0.001 and < 0.00000, respectively). Toxicity of thal was generally mild and well manageable. All patients but 7 continued planned daily thal and pulsed dex until the day before second Tx. Causes of thal discontinuation included deep vein thrombosis in a single patient, inadequate PBSC collection in 3 patients and granulocytopenia in 3 other patients. In conclusion, incorporation of thal-dex into a multiphase treatment program including CTX for PBSC collection and PBSC-supported MEL for newly diagnosed MM resulted in a significantly increased rate of CR + VGPR in comparison with the same treatments administered without added thal-dex. The objective of increasing the rate of ≥ VGPR by administering thal-dex following CTX and first Tx was achieved without the cost of increased toxicity. Whether these favorable results translated into extended overall survival still remains to be demonstrated; an analysis will be presented at the meeting.
Supported by Università di Bologna, Progetti di Ricerca ex-60% (M.C.); Ministero dell’Università e Ricerca Scientifica (MIUR), progetto FIRB, RBAU012E9A_001 (M.C.); and Fondazione Carisbo.