Lenalidomide After Autologous Transplantation for Myeloma: First Analysis of a Prospective, Randomized Study of the Intergroupe Francophone Du Myelome (IFM 2005 02).

Abstract 529

High dose therapy (HDT) supported with autologous stem cell transplantation is a standard treatment option for aggressive myeloma. However, after a single or a double transplantation, almost all patients ultimately relapse. Thus, new strategies are required to control the residual disease after HDT. We previously reported that Thalidomide administered after HDT was able to reduce this residual disease and to improve the EFS and the OS (IFM 99 02 trial). However, in this trial the high incidence of neuropathy induced by thalidomide (68%) was a major limiting factor. Lenalidomide, the analog of thalidomide without neurological toxicity, was thus an attractive drug to evaluate as consolidation/maintenance treatment after HDT.

From July 2006 to August 2008, 614 myeloma patients under the age of 65 years, with non progressive disease after a first line ASCT (performed less than 6 months before) were enrolled in the IFM 200502 protocol. Enrolled patients were to receive a consolidation treatment with lenalidomide (25 mg/d, po, 21 days/month, for 2 months) followed by a maintenance treatment with lenalidomide till relapse (10 to 15 mg/d) or a maintenance treatment with placebo till relapse.

Initial characteristics were the following one: age=56.5 y; stage DS: I=4%, II=17%, III=79%; beta-2 m=3.3 mg/l; FISH analysis: del 13 = 212/538, t 4-14 = 38/538, del 17p=47/538. The induction regimen was: VAD (48%), velcade/dex (46%), thal/dex (2%), or another regimen (4%). Patients received a single ASCT (79%) or a tandem ASCT (21%). The mean interval between ASCT and revlimid consolidation was 4 months (SD=1.3).

On July 2009, data from 542 patients, who received at least one dose of consolidation treatment with lenalidomide, were evaluable on an investigator based assessment. 435 patients (80%) could receive the planned 2 cycles of consolidation, 64 patients (12%) could receive the 2 cycles with a reduced dose, and 43 patients (8%) had to definitively discontinue lenalidomide (17 during the first cycle and 26 during the second one). The median number of days with consolidation was 42 d (range=2 to 42), the median cumulative dose of lenalidomide was: 1050 mg (range = 50 to 1050). During consolidation, 97 grade 3 or 4 SAE occurred in 74 patients: hematological events (n=46), allergic disorders (n=19), infections (n=7), fatigue (n=5), thromboembolic event (n=1), others (n=19).

Pre and post consolidation data were availabel for 412 patients. The response rate before consolidation was: sCR = 9 (2.2%), CR = 90 (22%), VGPR = 206 (50%), PR=104 (25%) and SD = 3 (0.7%). Among the 403 patients (sCR are excluded) with an evaluable tumor mass before consolidation, 60 patients (15%) upgraded their response after consolidation: 5 CR achieved sCR; 29 VGPR achieved CR (n=27) or sCR (n=2); 25 PR achieved VGPR (n=18) or CR (n=6) or sCR (n=1). Thus, lenalidomide consolidation was found to significantly improve the sCR/CR rate (p=0.0005; Mc Nemar's test).

Finally, our 2 month consolidation with lenalidomide was feasible (80% of patients could receive the planned 2 cycles of consolidation) and was found to significantly improve the sCR/CR rate. Monitored data, concerning this consolidation phase, for the 614 enrolled patients, reviewed by an Independent Review Committee will be presented during the meeting.