Daratumumab + bortezomib, thalidomide, and dexamethasone (D-VTd) in transplant-eligible newly diagnosed multiple myeloma (TE NDMM): Baseline SLiM-CRAB based subgroup analysis of CASSIOPEIA.

Abstract

8538 Background: In the phase 3 CASSIOPEIA study, D-VTd significantly improved outcomes vs VTd in TE NDMM pts at an 18.8-mo median follow-up. To allow earlier diagnosis and treatment of MM, the IMWG added 3 validated biomarkers (≥60% clonal bone marrow plasma cells, serum free light chain ratio ≥100, and > 1 focal bone lesion by MRI; “slim”) to the conventional “CRAB” diagnostic criteria. We present a subgroup analysis of CASSIOPEIA based on baseline slimCRAB criteria. Methods: TE NDMM pts were randomized 1:1 to 4 pre-ASCT induction and 2 post-ASCT consolidation cycles of D-VTd or VTd. The “slim-only” subgroup excludes pts with ≥1 conventional CRAB criterion based on data collected at baseline; the remaining pts were included in the “CRAB” subgroup. Results: Of 1085 randomized pts (543 D-VTd; 542 VTd), 81 were included in the slim-only subgroup (36 D-VTd; 45 VTd) and 1004 were included in the CRAB subgroup. In slim-only vs CRAB pts, 22% vs 54% had an ECOG score of ≥1, 4% vs 16% had ISS Stage III disease, and 11% vs 16% had high-risk cytogenetics. For D-VTd vs VTd pts in the slim-only group, these rates were 22% vs 22%, 8% vs 0%, and 6% vs 16%, respectively. Overall response rates (ORR) and rates of sCR, ≥CR, and MRD negativity were similar between slim-only and CRAB pts; for slim-only pts, rates were significantly higher for D-VTd vs VTd (Table). After an 18.8-mo median follow-up, progression-free survival (PFS) was not significantly different in slim-only vs CRAB pts, or in D-VTd vs VTd slim-only pts (Table). For D-VTd vs VTd CRAB pts, 18-mo PFS rates were 92% vs 84%, and 24-mo PFS rates were 89% vs 76%. Conclusions: Baseline characteristics indicate that slim-only pts were slightly fitter and of lower risk status vs CRAB pts; however, response rates, MRD-negativity rates, and PFS did not differ significantly between these groups. Among slim-only pts, significantly higher response and MRD-negativity rates were achieved with D-VTd vs VTd. Among CRAB pts, PFS rates were higher with D-VTd vs VTd. Clinical trial information: NCT02541383 . [Table: see text]