Professor Institut Universitaire du Cancer de Toulouse-Oncopole Toulouse, Midi-Pyrenees, France
Introduction: Previous results from CASSIOPEIA demonstrated superior MRD-negativity (neg) rates with D-VTd vs VTd induction/consolidation (ind/conso) and increased MRD-neg rates with DARA maintenance (maint) vs observation (OBS) in patients (pts) with transplant-eligible (TE) NDMM. Here we report long-term MRD outcomes.
Methods: In Part 1 of the phase 3 CASSIOPEIA trial (NCT02541383), pts were randomized 1:1 to 4 cycles of pre-ASCT ind and 2 cycles of post-ASCT conso with D-VTd or VTd. In Part 2, pts in partial response or better after conso were re-randomized 1:1 to DARA maint Q8W or OBS for £2 y. MRD was assessed for all pts regardless of response at the end of both ind and conso; in pts with very good partial response or better at 6, 12, and 24 mo during maint; and at 1, 2, and 3 y follow-up in pts who had not progressed and were MRD neg at last assessment. MRD data presented for ind/conso are by MFC only (10–5). MRD data for maint and follow-up at 10–5 used combined NGS/MFC results (MFC used only when NGS not available). MRD data presented for maint at 10–6 is by NGS only, due to limitations of MFC at this threshold.
Results: D-VTd improved overall MRD-neg rates (10–5) vs VTd at post ind (35% vs 23%; P< 0.0001) and post conso (64% vs 44%; P< 0.0001). During maint, overall MRD-neg rates were higher for pts who received DARA (D-VTd/DARA vs D-VTd/OBS: 10–5, 77% vs 71% [P=0.0417]; 10–6, 61% vs 52% [P=0.0365]; VTd/DARA vs VTd/OBS: 10–5, 71% vs 51% [P=0.0001]; 10–6, 48% vs 31% [P< 0.0001]). MRD-neg pts post ind had superior PFS outcomes; yet post-ind PFS was significantly improved in pts who received D-VTd vs VTd, whether they were MRD neg (HR 0.399; 95% CI, 0.271-0.586; P< 0.0001) or not (HR 0.741; 95% CI, 0.613-0.894; P=0.0018). Pts who achieved MRD neg post conso also had superior PFS; however, DARA maint offered benefit regardless of post-conso MRD status: DARA MRD neg vs OBS MRD neg (HR 0.544; 95% CI, 0.382-0.775; P=0.0007) and DARA MRD positive (pos) vs OBS MRD pos (HR 0.484; 95% CI, 0.387-0.604; P< 0.0001). An overlap in PFS was observed for MRD-pos pts who received DARA maint and MRD-neg pts in the OBS group. For overall MRD-neg rates and sustained MRD-neg rates (10–5 and 10–6), the highest rates were consistently observed at all measured timepoints in pts who received D-VTd/DARA, and rates were greater in pts who received DARA maint vs OBS within each respective ind/conso treatment group.
Conclusions: Data from this MRD analysis demonstrate that receiving D-VTd in both ind/conso and DARA maint resulted in the deepest and most durable MRD neg outcomes in TE pts with NDMM. Furthermore, receiving DARA maint offers PFS benefit regardless of MRD status. These data support the use of D-VTd ind/conso as a standard of care in TE NDMM pts and demonstrate the additional benefit of DARA monotherapy use during maint for up to 2 y.