Dr Corre on MRD Negativity With D-VTd Induction/Consolidation in Newly Diagnosed Multiple Myeloma

Jill Corre, PharmD, PhD, professor, Hematology Laboratory, the University Toulouse Hospital; the Cancer University Institute, Toulouse Oncopole, France, discusses the depth and durability of minimal residual disease (MRD) negativity following treatment with the induction and consolidation of daratumumab (Darzalex) plus bortezomib (Velcade), thalidomide (Thalomid), and dexamethasone (D-VTd) in newly diagnosed multiple myeloma.

The phase 3 CASSIOPEIA trial (NCT02541383) evaluated D-VTd as induction and consolidation therapy followed by daratumumab maintenance vs VTd and observation in patients with transplant-eligible, newly diagnosed multiple myeloma. Patients who achieved a partial response or better were further randomly assigned to receive daratumumab or observation during the maintenance phase.

Findings presented during the 21st IMS Annual Meeting revealed that MRD negativity rates were significantly higher with D-VTd compared with VTd, Corre reports. At a median follow-up of 80.1 months, D-VTd improved MRD negativity rates (10^-5) over VTd both post-induction (34.6% vs 23.1%; OR, 1.76; P <.0001) and post-consolidation (63.7% vs 43.7%; OR, 2.26; P <.0001). This benefit was observed across all subgroups, regardless of MRD status, emphasizing the importance of optimizing induction therapy in myeloma, Corre notes.

Daratumumab maintenance further increased MRD negativity rates, achieving deeper and more durable responses, Corre continues. Early MRD negativity was associated with superior progression-free survival (PFS) outcomes, she says. Importantly, daratumumab maintenance improved PFS regardless of post-consolidation MRD status or prior daratumumab exposure, and patients with high-risk cytogenetic abnormalities also benefited from daratumumab maintenance, Corre adds.

Throughout the study, D-VTd consistently yielded higher overall MRD negativity rates, especially among patients who received daratumumab during induction, consolidation, and maintenance, Corre notes. These patients showed the highest rates of sustained MRD negativity and the most favorable PFS outcomes. Corre highlights that even patients with persistent MRD positivity benefited from D-VTd, underscoring its efficacy across different MRD statuses. Overall, D-VTd provided substantial long-term benefits, including sustained MRD negativity and improved survival outcomes, solidifying its role as a key treatment regimen for transplant-eligible multiple myeloma, she concludes.