The treatment landscape for newly diagnosed multiple myeloma (NDMM) is evolving rapidly, with clinical trials such as PERSEUS, IsKia, and CASSIOPEIA offering valuable insights into novel therapeutic strategies. These trials address the need for improved depth of response and long-term survival in patients eligible for autologous stem cell transplantation (ASCT).
PERSEUS Trial: Daratumumab Plus VRd
The PERSEUS trial is evaluating the addition of daratumumab, a CD38-directed monoclonal antibody, to the standard bortezomib, lenalidomide, and dexamethasone (VRd) regimen in transplant-eligible NDMM patients. This Phase III study aims to determine if the combination of daratumumab with VRd (D-VRd) can improve outcomes compared to VRd alone. The rationale behind this approach is to leverage the synergistic effects of daratumumab with the established VRd regimen to achieve deeper and more durable responses. The trial's primary endpoint is progression-free survival (PFS), with secondary endpoints including overall survival (OS), minimal residual disease (MRD) negativity, and safety. Initial results suggest a significant improvement in PFS with the addition of daratumumab, potentially setting a new standard of care for transplant-eligible NDMM patients.
IsKia Trial: Isatuximab Plus Kd
The IsKia trial is investigating the combination of isatuximab, another CD38-directed monoclonal antibody, with carfilzomib and dexamethasone (Kd) in transplant-eligible NDMM. This study seeks to enhance the depth of response and progression-free survival compared to Kd alone. Isatuximab, like daratumumab, targets the CD38 protein on myeloma cells, inducing cell death through multiple mechanisms. By combining isatuximab with the potent proteasome inhibitor carfilzomib and dexamethasone, researchers aim to overcome resistance and achieve deeper remissions. The trial's primary endpoint is MRD negativity, a key indicator of long-term disease control. Secondary endpoints include PFS, OS, and safety. The results from IsKia could provide an alternative treatment option for transplant-eligible NDMM patients, especially those who may not be suitable for VRd-based regimens.
CASSIOPEIA Trial: Daratumumab Plus VTd
The CASSIOPEIA trial evaluated the addition of daratumumab to bortezomib, thalidomide, and dexamethasone (VTd) followed by daratumumab maintenance in transplant-eligible NDMM. The study demonstrated a significant improvement in overall survival with the addition of daratumumab to VTd induction therapy followed by daratumumab maintenance. The CASSIOPEIA trial established the benefit of incorporating daratumumab into the treatment paradigm for transplant-eligible NDMM, leading to its approval in this setting. The long-term follow-up data from CASSIOPEIA continue to support the use of daratumumab-based regimens in this patient population.
These trials collectively highlight the importance of incorporating novel agents, such as CD38-directed monoclonal antibodies, into the treatment of newly diagnosed multiple myeloma. The results from PERSEUS, IsKia, and CASSIOPEIA are shaping the evolving treatment landscape and offering the potential for improved outcomes for patients with this challenging disease.
