ASH 2020 | MRD negativity rates following carfilzomib, dex & dara in R/R myeloma
Ola Landgren, MD, PhD, Sylvester Comprehensive Cancer Center, University of Miami, FL, discusses an evaluation of measurable residual disease (MRD) negativity in relapsed/refractory multiple myeloma (MM) patients in the Phase III Candor Study (NCT03158688). The results of the study from over 400 patients found that carfilzomib, dexamethasone (dex) and daratumumab (dara) (KdD) was superior to Kd in terms of progression-free survival. MRD was measured by next-generation sequencing of bone marrow samples. At the 12-month analysis, MRD-negativity was higher in patients in complete remission receiving KdD than Kd (12.5% vs 1.3%). Additionally, MRD responses were deeper in the KdD arm than the Kd arm. These results support previous evidence of KdD’s efficacy in relapsed/refractory MM. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.
Transcript (edited for clarity)
The CANDOR study was published in the Lancet in the fall of 2020. This is the comparison of carfilzomib with daratumumab and dexamethasone versus carfilzomib and dexamethasone in relapsed/refractory patients with one to three prior lines of myeloma therapy.
Here at this presentation focusing on minimal residual disease negativity, we look at different strategies for capturing MRD. We look at the best overall MRD negativity at any time...
The CANDOR study was published in the Lancet in the fall of 2020. This is the comparison of carfilzomib with daratumumab and dexamethasone versus carfilzomib and dexamethasone in relapsed/refractory patients with one to three prior lines of myeloma therapy.
Here at this presentation focusing on minimal residual disease negativity, we look at different strategies for capturing MRD. We look at the best overall MRD negativity at any time. We also look at a fixed time point, which is one year after therapy so that’s the 12-month MRD negativity. We look specifically in patients who achieved CR and then we looked in broader context, independent of their serum response.
What we show is in the most conservative approach, the 12 months MRD negativity in CR patients that the three-drug combination carfilzomib-daratumumab-dexamethasone has 12.5% MRD negativity compared to 1.3% just with carfilzomib and dexamethasone.
As we do subanalysis looking at the best overall MRD response at any time, or we do different other sub-analysis, the best results we see is the best overall MRD negativity at any time, which was the three-drug combination is as high as 22.8% versus 5.8%, respectively.
I do think the reason why you see that the numbers are higher with little bit more liberal approaches is because there’s probably a delayed clearance of the serum protein in the blood. Although you can eradicate the cells in the bone marrow and prove that the patient is MRD negative, we have seen in others for a long time now, that you could have lingering monoclonal protein for quite extended period of time in the blood. So the patient may not fulfill the definition of a CR, but if you wait a few more months, the blood will clear and now you would see that the patient is in CR and MRD negativity.
So my prediction is that we will see continued deepening of MRD negativity as we continue to follow up. We will also do additional analysis so we will zoom in on subsets of patients with regard to high and standard risk disease in relation to MRD negativity.
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Disclosures
Consultancy: Adaptive, Amgen, Janssen, Glenmark, Celgene, Binding Site, BMS, Cellectis, Juno, Pfizer
Honoraria: Adaptive, Amgen, Janssen, Glenmark, Celgene, Binding Site, BMS, Cellectis, Juno, Pfizer
Research Funding: Amgen, Janssen, Takeda, Glenmark, Celgene, Seattle Genetics, Karyopharma
Independent Data Monitoring Committees for clinical trials: Janssen, Takeda
Other: Merck
