Author(s): P. L. McCarthy, K. Owzar, K. C. Anderson, C. C. Hofmeister, H. Hassoun, D. D. Hurd, E. A. Stadtmauer, S. Giralt, V. Hars, C. A. Linker, for CALGB, ECOG and BMT-CTN

ABSTRACT:

Background: Disease relapse/progression is the primary cause of treatment failure after ASCT for MM.

Methods: The primary objective of CALGB 100104 was to investigate if maintenance lenalidomide would prolong time to progression (TTP) following single ASCT. Eligibility included: Stage I-III disease, < 1 year from diagnosis, > 2 months of induction with Stable Disease or better ( > SD) and age < 70 years. ASCT regimen was melphalan 200 mg/m2. Patients (pts) with > SD were randomized double-blind at day 100-110 post-ASCT to lenalidomide or placebo until disease progression, after stratification by diagnostic ß-2 microglobulin (ß-2M) level and prior thalidomide or lenalidomide therapy. Starting dose was 10 mg/day, escalated to 15 mg/day after 3 months. Drug was held for > Gr 3 toxicity, restarted at resolution to < Gr 2 and was de- escalated by 5 mg or maintained at 5, 10 or 15 mg/day as tolerated.

Results: 568 pts were enrolled (04/15/05 - 07/03/09). The second interim analysis, based on 418 randomized pts occurred on 09/09 after 28% of the required number of events (progression or death before progression) had been observed. The median follow-up was 12 months. The number of events among 210 pts randomized to lenalidomide was 29 compared to 58 among 208 pts randomized to placebo. The one-sided unadjusted P-value was < 0.0001. The estimated hazard ratio was 0.42 (95% CI=0.27,0.67) corresponding to a 58% reduction in event risk in the lenalidomide arm. The estimated median TTP was 25.5 months for the placebo arm. The median TTP has not been reached for the study arm. Deaths in the study and placebo arms were 11 and 17 respectively (P=0.2). Significant delay in TTP in the lenalidomide arm was observed regardless of ß-2M level or prior thalidomide or lenalidomide therapy. For 285 reported pts, the post-randomization, highest grade, overall AEs were Gr 3 (n=19), Gr 4 (n=111) and Gr 5 (n=1) for the lenalidomide arm and Gr 3 (n=4) Gr 4 (n=115) and Gr 5 (n=1) for placebo. The majority of AEs were hematologic in both arms.

Conclusions: Lenalidomide initiated at day 100-110 post-ASCT in MM patients significantly delays TTP and has a similar AE profile when compared to placebo.