Multiple myeloma treatment has seen significant advancements in recent years. The CEPHEUS trial, presented at the 2024 International Myeloma Society Annual Meeting, highlights the potential of daratumumab (Darzalex)-based combination therapies. This article explores the trial’s design, key findings regarding minimal residual disease (MRD), and the impact on patient care, offering expert insights from Saad Usmani, MD, MBA.
Understanding the Impact of Daratumumab + VRd
Adding subcutaneous daratumumab to the standard bortezomib, lenalidomide, and dexamethasone (VRd) regimen aims to deepen treatment responses and improve survival outcomes for newly diagnosed multiple myeloma patients who are ineligible for or have deferred stem cell transplantation. This innovative approach builds on the proven success of VRd and the daratumumab, lenalidomide, and dexamethasone (DRd) combination from the MAIA trial.
CEPHEUS Trial Design and Endpoints
The CEPHEUS trial is a randomized phase 3 study comparing VRd alone to the daratumumab + VRd (D-VRd) quadruplet regimen. 395 newly diagnosed multiple myeloma patients were randomized to receive either VRd or D-VRd induction therapy. Maintenance therapy consisted of lenalidomide and dexamethasone (Rd) in the VRd arm and daratumumab, lenalidomide, and dexamethasone (DRd) in the D-VRd arm.
The trial’s primary endpoint was the overall MRD negativity rate. Secondary endpoints included progression-free survival (PFS), sustained MRD negativity for more than 12 months, complete response rate, and overall survival.
Significant Findings Related to MRD Negativity
The CEPHEUS trial demonstrated a significantly higher MRD negativity rate in the D-VRd arm. Using next-generation sequencing at 10⁻⁵ sensitivity, MRD negativity was achieved in approximately 61% of patients receiving D-VRd compared to 39.4% in the VRd arm, representing a substantial improvement of over 20%.
Impact on Progression-Free Survival and Other Secondary Endpoints
The D-VRd regimen also demonstrated a significant improvement in PFS. After a median follow-up of 58.7 months, the median PFS in the D-VRd arm had not yet been reached, while the median PFS in the VRd arm was 52.6 months. This translates to a hazard ratio of 0.57 and a p-value of 0.0005, indicating a substantial benefit for patients receiving the daratumumab-containing regimen.
Implications for Pharmacists and Patient Care
The CEPHEUS results solidify the role of daratumumab-based quadruplet and triplet therapies as standard of care for newly diagnosed, transplant-ineligible or transplant-deferred multiple myeloma patients. When counseling patients, pharmacists can emphasize the importance of these regimens in achieving deeper responses and improved PFS. The enhanced efficacy translates to better long-term outcomes for patients.
Daratumumab-Based Therapies: A New Standard of Care
The integration of CD38 monoclonal antibodies like daratumumab into frontline multiple myeloma treatment represents a significant advancement. These therapies are generally safe and effective, contributing to improved outcomes and offering new hope for patients facing this challenging disease. For personalized treatment plans, consult with a healthcare professional today.
