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 21st International Myeloma Society Annual Meeting 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; P < .0001) and post-consolidation (63.7% vs 43.7%; OR, 2.26; P < .0001) at a median follow-up of 80.1 months.

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.