Professor and Chairman of the Department of Clinical Therapeutics National and Kapodistrian University of Athens, Greece
Introduction: In PERSEUS, DARA + VRd induction/consolidation (ind/consol) and D-R maint improved progression-free survival (PFS) and increased rates of minimal residual disease (MRD) negativity and sustained MRD negativity vs VRd ind/consol and R maint in TE NDMM, regardless of cytogenetic risk status. We report an expanded analysis of PERSEUS (PFS, overall MRD negativity, and sustained MRD negativity) based on the presence of high-risk cytogenetic abnormalities (HRCAs), including gain(1q21) and amp(1q21).
Methods: TE patients (pts) with NDMM were randomly assigned 1:1 to D-VRd or VRd. Pts in both arms received up to six 28-day cycles (4 pre-ASCT ind, 2 post-ASCT consol) of VRd and R maint (until progressive disease [PD]). In the D-VRd arm, pts also received subcutaneous DARA QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W during maint until PD.
Cytogenetic risk was assessed by FISH. High risk was defined per protocol as the presence of ³1 of the following HRCAs: del(17p), t(4;14), t(14;16). Revised high risk was defined as the presence of ³1 of the following HRCAs: del(17p), t(4;14), t(14;16), gain(1q21), amp(1q21). Cytogenetic risk subgroups included standard risk (0 HRCAs; protocol definition); high risk (protocol definition); revised standard risk (0 HRCAs; revised definition); revised high risk; gain(1q21) and amp(1q21) (3 copies and ≥4 copies, respectively, of chromosome 1q21 ± other HRCAs); and (only) 1 HRCA and ≥2 HRCAs (revised definition). MRD-negativity rate was defined as the percentage of pts in ITT population who achieved both complete response or better and MRD negativity.
Results: 709 pts were randomized (D-VRd, n=355; VRd, n=354). At a median follow-up of 47.5 months, PFS favored D-VRd vs VRd across all cytogenetic risk subgroups.
Overall MRD-negativity rates (10–5) were higher with D-VRd vs VRd across subgroups: standard risk (77.3% vs 48.1%; P< 0.0001), high risk (68.4% vs 47.4%; P=0.0086), revised standard risk (75.3% vs 47.3%; P< 0.0001), revised high risk (73.1% vs 49.3%; P< 0.0001), gain(1q21) (69.5% vs 46.5%; P=0.0086), amp(1q21) (85.7% vs 55.6%; P=0.0104), 1 HRCA (75.3% vs 50.0%; P=0.0002), and ≥2 HRCAs (66.7% vs 47.4%; P=0.1044).
Rates of sustained MRD negativity (10–5) for ≥12 months were higher with D-VRd vs VRd across subgroups: standard risk (69.3% vs 31.2%; P< 0.0001), high risk (48.7% vs 25.6%; P=0.0032), revised standard risk (66.1% vs 31.7%; P< 0.0001), revised high risk (59.2% vs 27.7%; P< 0.0001), gain(1q21) (62.7% vs 29.6%; P=0.0002), amp(1q21) (71.4% vs 27.8%; P=0.0006), 1 HRCA (61.9% vs 28.2%; P< 0.0001), and ≥2 HRCAs (51.5% vs 26.3%; P=0.0303).
Results for additional cytogenetic risk subgroups will be presented.
Conclusions: DARA plus VRd ind/consol and R maint improved PFS and induced higher rates of deep and sustained responses vs VRd ind/consol and R maint across all cytogenetic risk subgroups. These data support D-VRd ind/consol and D-R maint as a new standard of care for TE NDMM, regardless of cytogenetic risk status.
