Daratumumab-Based Regimens Deepen Responses and Improve MRD Negativity in Multiple Myeloma
核心洞察
Daratumumab plus lenalidomide maintenance significantly increased MRD-negative conversion rates compared to lenalidomide alone in transplant-eligible newly diagnosed multiple myeloma (搜索) patients.
The addition of daratumumab to VRd improved MRD negativity rates in transplant-ineligible or deferred newly diagnosed multiple myeloma (搜索) patients.
D-VRd followed by D-R maintenance resulted in higher rates of overall MRD-negativity in revised high-risk multiple myeloma (搜索) subgroups.
Data from multiple studies presented at the International Myeloma Society (IMS) Annual Meeting and other conferences demonstrate the clinical efficacy of daratumumab-based regimens in improving minimal residual disease (MRD) negativity and progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (搜索) (NDMM).
Daratumumab Plus Lenalidomide Maintenance Improves MRD Negativity
The phase 3 AURIGA study (NCT03901963) evaluated subcutaneous daratumumab plus lenalidomide (D-R) versus lenalidomide (R) alone as maintenance therapy in NDMM patients who were MRD-positive post-autologous stem cell transplant (ASCT). The study found that D-R significantly increased MRD-negative conversion rates at 12 months compared to R alone (50.5% vs 18.8%, P < .0001).
According to Dr. Ashraf Badros, professor of medicine at the University of Maryland School of Medicine, "Combining DARZALEX FASPRO with lenalidomide in the maintenance setting offers an advantage over lenalidomide alone for patients who are newly diagnosed with multiple myeloma (搜索) and anti-CD38 (搜索) naïve."
The increased MRD-negative conversion rate resulted in a PFS favoring D-R (HR, 0.53; 95% CI, 0.29-0.97) with an estimated 30-month rate of 82.7% compared to 66.4% for the R arm. Grade 3/4 treatment-related adverse events (TRAEs) were slightly more common with D-R (74%) compared to R (67.3%).
D-VRd Improves MRD Negativity in Transplant-Ineligible Patients
The phase 3 CEPHEUS trial (NCT03652064) investigated the addition of daratumumab to bortezomib, lenalidomide, and dexamethasone (VRd) in patients with newly diagnosed multiple myeloma (搜索) who were transplant-ineligible or for whom transplant was not intended as initial therapy. The study met its primary endpoint, demonstrating improved MRD-negativity rates at a sensitivity level of 10–5 among patients treated with D-VRd (60.9%) vs VRd alone (39.4%, P < .0001).
Saad Z. Usmani, MD, MBA, FACP, FASCO, chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center in New York, noted that the data support the use of either a daratumumab-based quadruplet or triplet as the standard of care for patients who are transplant-ineligible or who deferred transplant.
PERSEUS Trial: D-VRd Followed by D-R Maintenance
Expanded analyses of the Phase 3 PERSEUS study (NCT03710603) showed that daratumumab in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) in induction/consolidation followed by a maintenance regimen of D-R induced deep and sustained MRD-negativity compared to VRd regardless of disease stage based on the second revised International Staging System (R2-ISS).
In the revised high-risk subgroup, treatment with D-VRd followed by D-R maintenance results in higher rates of overall MRD-negativity at 10-6 with complete response or better compared to VRd (63.1 percent vs 32.4 percent; P <0.0001) with sustained MRD-negativity status for at least 12 months (42.3 percent vs 15.5 percent; P =0.0007).
CASSIOPEIA Trial: Daratumumab in Induction, Consolidation, and Maintenance
Updated MRD data from the Phase 3 CASSIOPEIA study (NCT02541383) demonstrate that including daratumumab in both induction/consolidation and maintenance regimens resulted in deeper and more durable MRD-negative responses at 10-5 level vs bortezomib/thalidomide/dexamethasone (VTd) and observation: 77 percent vs 71 percent (P =0.0417).
The benefit of daratumumab monotherapy maintenance was demonstrated in both patients who received VTd induction and consolidation, as well as those who received daratumumab and VTd. Daratumumab maintenance reduced the risk of progression or death by 24% in patients who received daratumumab and VTd as induction and consolidation.
These studies collectively highlight the significant benefit of incorporating daratumumab into various treatment regimens for multiple myeloma (搜索), leading to deeper responses, improved MRD negativity, and prolonged progression-free survival.