Dr Corre on the Clinical Implications of D-VTd Treatment in Newly Diagnosed Myeloma

Jill Corre, PharmD, PhD, professor, Hematology Laboratory, University Toulouse Hospital; Cancer University Institute, Toulouse Oncopole, discusses the clinical implications of findings with daratumumab (Darzalex) plus bortezomib (Velcade), thalidomide (Thalomid), and dexamethasone (D-VTd) in patients with newly diagnosed multiple myeloma.

Minimal residual disease (MRD) negativity rates following treatment with this combination in this patient population were evaluated in the phase 3 CASSIOPEIA trial (NCT02541383), and results from the investigation were presented at the 21st International Myeloma Society Annual Meeting. MRD negativity rates were significantly higher with D-VTd compared with VTd alone. In the D-VTd group (n = 543), MRD negativity was achieved at a sensitivity of 10–5, outperforming the VTd group (n = 542) both after induction therapy (34.6% vs 23.1%; odds ratio [OR], 1.76; P < .0001) and post-consolidation (63.7% vs 43.7%; OR, 2.26; P < .0001) at a median follow-up of 80.1 months.

To note, the coprimary end points were the stringent complete response rate after consolidation therapy and progression-free survival (PFS) following maintenance. Secondary end points included PFS, time to progression, and overall survival.

Corre states that a key takeaway from the trial is that it established the quadruplet regimen as the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma, demonstrating that an anti-CD38 antibody can be incorporated into maintenance therapy, particularly for high-risk patients who may benefit from intensified treatment. Additionally, the trial highlights the value of MRD assessment, especially post-induction, as achieving MRD negativity at this stage is preferable, even if MRD negativity is reached after consolidation, she reports.

This trial’s findings underscored the critical importance of induction therapy and led to the initiation of the phase 3 MIDAS trial (NCT04934475), which adjusts treatment with another quadruplet regimen, isatuximab plus bortezomib, lenalidomide (Revlimid), and dexamethasone, in patients with multiple myeloma based on MRD status after induction. The results of this ongoing trial will reveal whether this adaptive approach offers additional benefits for patients with myeloma, she concludes.