A randomized Southwest Oncology Group study comparing dexamethasone (D) to lenalidomide + dexamethasone (LD) as treatment of newly-diagnosed multiple myeloma (NDMM): Impact of cytogenetic abnormalities on efficacy of LD, and updated overall study results

Abstract

8521 Background: We recently reported superior 1-yr prog. free survival (PFS) for pts with NDMM treated with LD vs D alone. High-risk cytogenetic abnormalities (HRCA) confer poor prognosis with standard therapies, including high dose melphalan. It is unknown if pts on LD with HRCA will also have inferior results. We prospectively examined the impact of abnormal karyotype (AK) and HRCA (defined as deletion of chromosomes 13 and/or 17 by FISH) on 1-yr PFS and overall survival (OS), as well as updated overall study results. Methods: 198 pts with NDMM were randomized to L 25 mg/day (28 of 35 days x 3 cycles, then 21 of 28 days as maintenance) + D (40 mg d1–4, 9–12, 17–20 induction; d1–4, 15–18 maintenance) or D (same induction and maintenance schedules) + placebo. Cross-over to LD was allowed for progressive disease on D. Aspirin 325 mg/d was mandated. Pts had a baseline bone marrow aspirate for karyotypic analysis and FISH for deletions of chromosomes 13 and 17. The response rate (RR) by IMWG criteria, PFS, and OS of pts in each study arm were updated. The impact of AK and HRCA by FISH on PFS and OS was assessed by log-rank analysis. Results: Informative baseline karyotypes and FISH results were available for 103 and 80 pts, respectively. AK were seen in 10/52 samples from pts on D, and 11/51 on LD. Twelve of 45 samples from pts on D and 8/35 on LD had HRCA. For pts on LD without AK, 1-yr PFS and OS were 86% and 97% respectively, vs 55% (p=0.13) and 82% (p=0.02) in pts with AK. Pts on D alone with AK had 1-yr PFS and OS of 33% and 77% (p=NS). 1-yr PFS and OS for pts on LD were both 100% with HRCA vs 73% and 92% without HRCA (p=NS). Conclusions: In this sub-group analysis, pts with NDMM on LD with AK had lower PFS and OS compared to those without AK. HRCA as defined in this study did not seem to account for this difference, but sample size limited the statistical power of the analysis. Pts with AK treated with LD had higher PFS and OS compared to those on D alone. Further characterization of observed karyotypic and FISH abnormalities, as well as extended follow-up for PFS, OS, and RR (including ≥VGPR rates) for S0232 will be presented at ASCO. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene, Millennium Celgene, Millennium