Darzalex Phase III CASSIOPEIA Trial Demonstrates Significant Improvement in Progression-Free Survival and Response Rates in Transplant-Eligible Newly Diagnosed Multiple Myeloma Patients

On June 2, Xian Janssen, a subsidiary of Johnson & Johnson, presented for the first time at the ASCO Annual Meeting the data from the pivotal Phase III CASSIOPEIA clinical study evaluating Darzalex (daratumumab), a blockbuster CD38-targeted anticancer drug, in the treatment of multiple myeloma (MM). This is one of the largest transplant studies conducted in patients with MM and the largest-scale study of Darzalex to date.

The results showed that, among newly diagnosed multiple myeloma (MM) patients eligible for autologous stem cell transplantation (ASCT), adding Darzalex to the bortezomib + thalidomide + dexamethasone triplet regimen (VTd) before and after transplantation improved response rates and prolonged progression-free survival (PFS) compared with the standard VTd therapy.

CASSIOPEIA is a randomized, open-label, multicenter study that enrolled 1,085 patients with newly diagnosed multiple myeloma (MM) who were eligible for high-dose chemotherapy and stem cell transplantation. In Part 1 of the study, patients were randomized into two groups to receive induction therapy with either VTd or Darzalex plus VTd, followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), and consolidation therapy with either VTd or Darzalex plus VTd. The primary endpoint was the proportion of patients achieving a stringent complete response (sCR). Patients who achieved a partial response or better proceeded to Part 2 of the study.

Part 2 of the study is currently ongoing. In this part, patients undergo a second randomization to either receive Darzalex (16 mg/kg every 8 weeks) as maintenance therapy for up to two years or to be observed without further treatment. The primary endpoint is progression-free survival (PFS).

The results from the first part of the study showed that, after consolidation therapy, the proportion of patients achieving a stringent complete response (sCR) was significantly higher in the Darzalex + VTd group than in the VTd group (29% vs. 20%; OR = 1.60, 95% CI: 1.21–2.12; p < 0.0010). With a median follow-up of 18.8 months, progression-free survival (PFS) was significantly prolonged in the Darzalex + VTd group (HR = 0.47, 95% CI: 0.33–0.67; p < 0.0001), and the median PFS was not reached in either group. The 18-month PFS rate was 93% in the Darzalex + VTd group versus 85% in the VTd group.

Compared with the VTd group, a higher proportion of patients in the Darzalex + VTd group achieved a very good partial response or better (83% vs 78%; OR=1.41; 95% CI: 1.04–1.92; p=0.0239), a complete response or better (39% vs 26%; OR=1.82; 95% CI: 1.40–2.36; p<0.0001), and minimal residual disease negativity (sensitivity threshold 10⁻⁵: 64% vs 44%).

Regarding safety, the most common (≥10%) grade 3/4 treatment-emergent adverse events in the Darzalex+VTd and VTd groups were: neutropenia (28% vs. 15%), lymphopenia (17% vs. 10%), stomatitis (13% vs. 16%), and thrombocytopenia (11% vs. 7%). In the Darzalex+VTd group, 35% of patients experienced infusion-related reactions.

Based on the aforementioned research findings, Janssen submitted a new indication application for Darzalex to the U.S. FDA and the European EMA in March this year, for use in combination with standard therapy as first-line treatment for newly diagnosed multiple myeloma (MM) patients who are eligible for transplantation.

Darzalex is the first globally approved CD38-mediated, cytolytic antibody drug with broad-spectrum cytotoxic activity. It targets and binds to the CD38 molecule, a transmembrane ectoenzyme highly expressed on the surface of multiple myeloma cells and various solid tumor cells. Furthermore, Darzalex has been demonstrated to target immunosuppressive cells within the tumor microenvironment, thereby exhibiting immunomodulatory activity.

Darzalex is a product vigorously developed by Johnson & Johnson, which has been approved for first-line treatment of newly diagnosed multiple myeloma (MM) in patients ineligible for transplantation, as well as for second-line and later-line treatment of MM. In addition, the drug also shows potential for treating other types of tumors with high CD38 expression, including diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, plasma cell leukemia, acute myeloid leukemia, follicular lymphoma, and mantle cell lymphoma.

In 2018, Darzalex’s global sales reached $2.025 billion, representing a year-over-year increase of 63.0%. EvaluatePharma predicts that Darzalex’s global sales will reach $6.033 billion in 2024, making it a key product driving Johnson & Johnson’s future growth.

Reference Source: Study Investigating Darzalex® (daratumumab) Shows Improved Depth of Response and Progression-Free Survival in Patients with Newly Diagnosed Multiple Myeloma Who are Eligible for a Transplant