Jill Corre, PharmD, PhD, discusses the implications of using daratumumab plus bortezomib, thalidomide, and dexamethasone in newly diagnosed myeloma.

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; 

 < .0001) and post-consolidation (63.7% vs 43.7%; OR, 2.26; 

 < .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.

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Dr Corre on the Rationale for the CASSIOPEIA Trial in Newly Diagnosed Myeloma

Jill Corre, PharmD, PhD, professor, Hematology Laboratory, University Toulouse Hospital; Cancer University Institute, Toulouse Oncopole, discusses the rationale for launching 

the phase 3 CASSIOPEIA trial (NCT02541383)

 of daratumumab (Darzalex) plus bortezomib (Velcade), thalidomide (Thalomid), and dexamethasone (D-VTd) in patients with newly diagnosed multiple myeloma.

Notably, Corre and coinvestigators evaluated the depth and durability of minimal residual disease (MRD) negativity following treatment with induction and consolidation D-VTd regimens in patients with multiple myeloma. Findings were presented at the 

 and showed that with D-VTd treatment, MRD negativity rates were significantly higher compared with VTd alone. D-VTd (n = 543) improved MRD negativity rates at a sensitivity of 10–5 vs VTd (n = 542) both post-induction (34.6% vs 23.1%; odds ratio [OR], 1.76; 

The CASSIOPEIA trial randomly assigned patients with newly diagnosed myeloma to receive induction and consolidation treatment with either D-VTd or VTd alone, Corre begins. Patients who achieved a partial response or better were then randomly assigned in the second phase of the trial to receive either daratumumab maintenance therapy or undergo observation for up to 2 years, she explains. The trial has established D-VTd as a standard treatment for newly diagnosed, transplant-eligible patients with myeloma, she expands.

To be eligible for enrollment, patients had to have previously untreated multiple myeloma, be candidates for high-dose chemotherapy and autologous stem cell transplantation, and have an ECOG performance status between 0 and 2. Patients with primary amyloidosis, plasma cell leukemia, or smoldering multiple myeloma were excluded. The coprimary end points were stringent complete response rate following consolidation therapy and progression-free survival (PFS) after maintenance therapy. Secondary end points included PFS, time to progression, and overall survival.

Long-term follow-up results from the maintenance phase have further demonstrated that patients who received D-VTd followed by daratumumab maintenance experienced the longest median PFS compared with other groups, Corre reports. This reinforces the role of daratumumab, both in induction therapy and as a maintenance option, in prolonging disease control and improving outcomes in this patient population, she concludes.

Jill Corre, PharmD, PhD, discusses the CASSIOPEIA trial of daratumumab plus bortezomib, thalidomide, and dexamethasone in newly diagnosed myeloma.

Jill Corre, PharmD, PhD, discusses minimal residual disease negativity rates after treatment with D-VTd induction/consolidation in newly diagnosed multiple myeloma.

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.

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

) over VTd both post-induction (34.6% vs 23.1%; OR, 1.76; 

 <.0001) and post-consolidation (63.7% vs 43.7%; OR, 2.26; 

 <.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.

Jill Corre, PharmD, PhD

Articles

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

Dr Corre on the Rationale for the CASSIOPEIA Trial in Newly Diagnosed Myeloma

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