(PA-452) Interim Analysis of DARA VRD in the Treatment of TE-NDMM Patients with Standard Risk Who Refused to Accept ASCT as First Line in China

In China, ASCT as front-line therapy is merely 10%. Studies, such as GRIFFIN (D-VRd) and CASSIOPEIA (D-VTd), have shown promising results in TE-NDMM patients receiving ASCT as initial therapy.These findings have prompted us to investigate the potential efficacy of D-VRd in standard-risk patients.This interim analysis presents the first open-label, single-arm study evaluating the efficacy and safety of D-VRd in TE-NDMM patients with standard risk who declined ASCT in China (NCT 05088330).

Methods:

We enrolled IMWG-defined NDMM patients,who were TE but voluntarily declined ASCT,excluding those with t(4;14), Del(17p), t(14;16), R-ISS stage III.The D-VRd regimen consisted:Daratumumab:16 mg/kg I.V. weekly for 2 cycles, then every 3 weeks for 6 more cycles,bortezomib:1.3 mg/m2 SC,Days 1, 4, 8, 11,lenalidomide:25 mg P.O.,Days 1-14,dexamethasone:20 mg P.O.,Days 1, 2, 4, 5, 8, 9, 11, 12.All for 8 cycles, followed by daratumumab maintenance:16mg/kg q4w×12mo.The primary endpoint was NGS MRD negativity at 10^-5 after 8 cycles of D-VRd.Secondary objectives included ORR,sCR,≥CR,≥VGPR, AEs,TTR, and DOR.Stem cell collection advised post-Cycle 4.

Results:

 By June 30, 2024, 46 pts were enrolled.The median age was 62 years, with 23 male pts. Cytogenetic analysis revealed 27 patients with 1q gain and 4 pts with t(11;14). Additionally, 8 pts presented with renal insufficiency, and 6 had EMD. The ORR was 97.4%, with 89.7% of pts achieving VGPR or better. Notably, 64.1% of patients attained CR or sCR. The median treatment duration was 10 months and median treatment cycles was 9.19 pts successfully underwent autologous stem cell collection and storage. With a median follow-up of 12 months, 72.7% of pts achieved NGS MRD negativity after 8 cycles. Subgroup analysis comparing pts with 1q gain versus those without showed ORR, CR+sCR, and 1-year progression-free survival rates of 95.8%, 58.3%, and 88.2% versus 100%, 73.3%, and 100%, respectively (p >0.01). Treatment-related adverse events primarily consisted of hematological toxicities, occurring in all 46 pts.These included thrombocytopenia in 80.4% (n=37; 22 Grade 1-2, 15 Grade 3-4), lymphopenia in 58.7% (n=27; 17 Grade 1-2, 10 Grade 3-4), and neutropenia in 43.4% (n=20;9 Grade 1-2, 11Grade 3-4) of pts. Other adverse events included ALT/AST elevation in 43.4% (n=20; 19 Grade 1-2, 1 Grade 3-4) and peripheral neuropathy in 45.7% (n=21;12 Grade 1-2, 9 Grade 3-4) of pts. Infusion-related reactions were reported in 23.9% of pts (n=11,all Grade 1-2). Pneumonia occurred in 13.0% of pts (n=6,all Grade 3),with all cases resolving.One patient discontinued lenalidomide due to pulmonary embolism.

Conclusions: Interim analysis shows D-VRd induces rapid, deep responses in Chinese TE-NDMM patients declining ASCT (including1q gain). High NGS MRD negativity (72.7%) pre-maintenance underscores efficacy. Hematological toxicities (most common AEs) were manageable after cycle 2, supporting acceptable safety.These results warrant further long-term evaluation.