Results of total therapy 2 (TT 2), a phase III randomized trial, to determine the role of thalidomide (THAL) in the upfront management of multiple myeloma (MM).

LBA6502 Background: Given the marked activity of THAL in end-stage MM, TT2 was designed (1) to determine THAL's activity in the context of intensive induction, tandem autotransplants, consolidation and maintenance therapies; and (2) to determine the prognostic implications of serial MRI and gene expression profiling (GEP).,Consenting patients with newly diagnosed active MM, stratified by B2M (<4mg/L, ≥4mg/L) and plasma cell labeling index (PCLI) (<1%, ≥1%), were randomized to receive either THAL or no THAL (applied throughout until relapse). Eligible patients were less than 75yr of age and had SWOG PS <3. The primary endpoint was an increase in 5-yr EFS from 40% to 50% in the THAL arm. Planned sample size of 668 patients gives 80% power, using a 2-sided test with a 0.045 significance level. This study was a prospective, randomized, stratified phase III trial. Survival data comparing THAL vs no THAL will be compared using a stratified log-rank test. Independent DSMB committee has approved release of results in March 2005.,Of 668 eligible patients, 345 were randomized to no THAL and 322 to THAL. The current median follow-up is 33 mos (range 9-73). Following 4 cycles of intensive induction chemotherapy, 85% completed 1st and 67% 2nd autotransplant with MEL 200; 64% started consolidation. 602 patients had a baseline MRI exam with a median of 4 follow-up exams. 351 patients, consecutively enrolled since March 2000, also had baseline GEP. Patient characteristics: age ≥60yr, 39%; male, 59%; karyotype abnormalities, 33%; B2M ≥4mg/L, 31%; albumin <3.5gd/L, 15%; LDH ≥190U/L, 30%; IgA isotype, 24%; PCLI ≥1%,14%. Overall 1yr TRM was 1.4%; overall n-CR/CR was 67% with 47% achieving a CR. DVT >3° frequency was significantly higher with THAL vs no THAL (34% vs 16%, p<.0001), but was markedly reduced after introduction of LMWH (24% vs 15%, p=.06). Peripheral neuropathy also was significantly more common with THAL (sensory: 12% vs 4%, p=.001; motor: 21% vs 13%, p=.01). Updated survival by arm will be presented prior to the late breaking abstract deadline. In addition, GEP and MRI data will be presented in the context of survival.,To be reached after data become available. [Table: see text].