Janssen's Darzalex-VTd Combination Therapy Receives Priority Review for Significantly Improving PFS in Newly Diagnosed Multiple Myeloma

Recently, Janssen, a subsidiary of Johnson & Johnson, announced positive results from a Phase 3 trial of its blockbuster monoclonal antibody drug Darzalex (daratumumab) in combination with bortezomib, thalidomide, and dexamethasone (also known as the Darzalex-VTd regimen) for multiple myeloma at the ASCO Annual Meeting. These trial results were simultaneously published in The Lancet.

Multiple myeloma is a malignant hematologic cancer caused by the malignant transformation of plasma cells in the bone marrow. It is estimated that in 2018, more than 30,000 individuals in the United States will be diagnosed with this disease, and approximately 13,000 will die from it. Current mainstay treatment regimens for multiple myeloma include chemotherapy, immunomodulatory drugs (IMiDs, such as lenalidomide), and/or proteasome inhibitors (PIs, such as bortezomib), with or without stem cell transplantation.

As a blockbuster monoclonal antibody targeting CD38, Darzalex specifically recognizes CD38, which is highly expressed on malignant plasma cells in multiple myeloma, with high affinity, thereby inducing tumor cell death through various immune-mediated mechanisms.

▲Schematic Diagram of the Mechanism of Action of Darzalex (Image source: Darzalex official website)

In the phase 3 CASSIOPEIA trial, researchers enrolled 1,085 patients with newly diagnosed, untreated multiple myeloma who were eligible for high-dose chemotherapy and stem cell transplantation. The trial consisted of two phases: initial treatment and consolidation therapy.

During the initial treatment phase, patients were randomized to receive either Darzalex-VTd or VTd alone in conjunction with high-dose chemotherapy and autologous stem cell transplantation (ASCT). In the post-transplant consolidation phase, patients continued to receive either Darzalex-VTd or VTd alone. The trial met its primary endpoint: the rate of stringent complete response (sCR) was significantly higher with Darzalex-VTd than with VTd alone (29% vs. 20%). At a median follow-up of 18.8 months, progression-free survival (PFS) was also improved in the Darzalex-VTd group compared with the VTd group. The median PFS has not yet been reached in either group; the proportion of patients achieving 18-month PFS was 93% in the Darzalex-VTd group versus 85% in the VTd group.

Following consolidation therapy, the Darzalex-VTd group demonstrated a higher rate of “very good partial response or better” compared with the VTd group (83% vs. 78%), a higher complete response rate (39% vs. 26%), and a higher minimal residual disease (MRD) negativity rate (64% vs. 44%).

Dr. Philippe Moreau, Head of the Hematology Department at Nantes University Hospital in France and one of the principal investigators of the CASSIOPEIA trial, stated: “CASSIOPEIA is the first trial to evaluate the clinical benefits of combining Darzalex with standard treatment regimens in patients with newly diagnosed multiple myeloma who undergo autologous stem cell transplantation (ASCT). There is a need for new first-line therapy options for newly diagnosed patients. The trial data on the Darzalex-VTd combination regimen provide further robust evidence supporting the use of Darzalex as a first-line therapy.”

References:

[1]. DARZALEX® (daratumumab) Investigational Study Shows Increased Depth of Response and Longer Progression-Free Survival in Patients with Newly Diagnosed Multiple Myeloma Who are Eligible for a Transplant. Retrieved June，2, 2019, from https://www.janssen.com/us/sites/www_janssen_com_usa/files/darzalexr_daratumumab_investigational_study_shows_increased_depth_of_response.pdf

[2]. Flash Update | Phase 3 Results of Multiple Myeloma Therapy Show Positive Outcomes, Reducing Risk of Disease Progression by 45%. Retrieved June 2, 2019, from https://mp.weixin.qq.com/s/fNYXVfOPEhdCuYceFI83Eg

[3]. Express | New Combination Therapy for Multiple Myeloma Approved by FDA. Retrieved June 2, 2019, from https://mp.weixin.qq.com/s/q6o4l8AUodWYDKmjpaZE1A

Original Title: ASCO | Significant Improvement in PFS, Janssen’s New Therapy Granted Priority Review Status

▽Follow [WuXi AppTecDe】WeChat Official Account