This article is more than 5 years old. Information may no longer be current.
Daratumumab associated with deep clinical response in relapsed, refractory multiple myeloma
Click Here to Manage Email Alerts
SAN DIEGO — The addition of daratumumab to standard-of-care therapies for relapsed or refractory multiple myeloma conferred significant reductions in minimal residual disease, according to an analysis of the POLLUX and CASTOR studies presented at the ASH Annual Meeting and Exposition.
To evaluate the ability of daratumumab (Darzalex, Janssen) to yield deep clinical responses beyond complete remission, Hervé Avet-Loiseau, MD, head of Laboratory for Genomics in Myeloma at University Cancer Center of Toulouse in France, and colleagues prospectively evaluated minimal residual disease (MRD) data from patients enrolled on the POLLUX and CASTOR studies.
“MRD is a more sensitive measure of disease burden,” Avet-Loiseau said. “It has been shown in several meta-analyses that achievement of MRD negativity is associated with prolonged PFS and OS. In the future, it may be a primary endpoint for clinical studies.”
In the POLLUX study, researchers evaluated the addition of daratumumab to lenalidomide (Revlimid, Celgene) and dexamethasone. Researchers of the CASTOR trial evaluated the addition of daratumumab to bortezomib (Velcade, Takeda Oncology) and dexamethasone.
Researchers assessed MRD at the time of suspected complete response in both studies, and then at 3 and 6 months after then in the POLLUX study and at 6 and 12 months after the first dose in the CASTOR study. Researchers assessed MRD on bone marrow aspirate samples with the ClonoSEQ assay (Adaptive Biotechnologies) at sensitivities of 0.01% (1 cancer cell per 10,000 nucleated cells, or 10-4), 0.001% (10-5), and 0.0001% (10-6).
The proportion of patients with negative MRD at any time point after the first dose determined the MRD negative rate per treatment arm.
Median follow-up was 13.5 months for the POLLUX study and 7.4 months for the CASTOR study.
At a sensitivity threshold of 10-4, the MRD negativity rate was 31.8% in the daratumumab arm and 8.8% in the non-daratumumab arm of the POLLUX study, and 18.3% in the daratumumab arm and 3.6% in the non-daratumumab arm of the CASTOR study.
At a threshold of 10-5, daratumumab yielded higher negative MRD rates in both the POLLUX (24.8% vs. 5.7%) and CASTOR (10.4% vs. 2.4%) studies. This trend persisted at a sensitivity threshold of 10-6 in POLLUX (11.9% vs. 2.5%) and CASTOR (4.4% vs. 0.8%).
“MRD negativity was consistently higher in patients treated in daratumumab,” Avet-Loiseau said, adding that patients treated with the drug reached MRD negativity as soon as 3 months. “We still see patients achieving MRD negativity.”
High-risk patients also achieved MRD negative status in both studies, according to Avet-Loiseau. Eighteen percent of high-risk patients in the POLLUX study and 14% of those in CASTOR achieved MRD negativity.
“The most important factor in achieving PFS is MRD negativity,” Avet-Loiseau said.
Further, daratumumab induced MRD negativity in three times as many patients as those treated with standard-of-care regimens.
“Daratumumab led to rapid and durable achievement of MRD negativity,” Avet-Loiseau said. “Patients continue to achieve MRD negativity over time. The high rate of MRD negativity may lead to long-term clinical benefit. The magnitude of daratumumab-induced MRD negativity in the relapsed or refractory multiple myeloma setting is unprecedented.” – by Rob Volansky
Reference:
Avet-Loiseau H, et al. Abstract 246. Presented at: The ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.
Disclosure: Avet-Loiseau reports speakers bureau roles with and honoraria and research funding from Amgen, Bristol-Myers Squibb, Celgene, Janssen and Sanofi. Please see the abstract for a list of all other researchers’ relevant financial disclosures.
Perspective
Back to Top
Noopur Raje, MD
It is amazing to see that we can get MRD negativity in the relapsed space. Both of these combinations were approved in November.
Perspective
Back to Top
Shaji Kumar, MD
Minimal residual disease (MRD) testing has become a standard assessment with the revised International Myeloma Working Group response criteria and was necessitated by the increasing efficacy of new therapies. These two trials are the first to evaluate MRD in the setting of relapsed disease. In the two studies, a high rate of MRD negativity has been observed, which has translated to longer PFS. The results are a testament to the efficacy of the drug in myeloma.
Click Here to Manage Email Alerts