Adaptive Biotechnologies, the leader in combining next-generation sequencing (NGS) and expert bioinformatics to profile T-cell and B-cell receptors of the adaptive immune system, and collaborators from the Dana-Farber Cancer Institute and University Hospital in Toulouse, France have presented data showing that Adaptive's NGS-based MRD assessment method (available for clinical use through Adaptive's CLIA-certified laboratory as the clonoSEQ® Process) sensitively detects minute traces of myeloma in clinical trial patients and predicts outcomes better than flow cytometry, supporting the use of the technique as a surrogate endpoint.
"With current intensive approaches to the treatment of myeloma, complete response rates are regularly achieved in the range of 50-70 percent, making conventional evaluations of response less helpful in clinical trials," said Nikhil Munshi, M.D., Director of Basic and Correlative Science, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, and a lead investigator on the study being presented at the 57th Annual Meeting of the American Society of Hematology Meeting in Orlando, FL. "More sensitive tools for evaluating response will be necessary moving forward in clinical trial development, and in this study we showed that NGS-based minimal residual disease measurement is an attractive choice."
The IFM/DFCI 2009 trial was designed to determine whether in the era of novel drugs, high dose therapy followed by autologous transplant is still necessary in the initial management of multiple myeloma in younger patients (<66 years old). Bone marrow samples taken before maintenance therapy were analyzed for MRD using Adaptive's technology in a total 246 patients. Samples taken after maintenance were analyzed for 178 patients.
There was a significant difference in the number patients who lived for three years without their disease getting worse [3-year progression-free survival (PFS)] when comparing MRD-negative and positive patients (sensitivity cutoff of one myeloma cell per one million white blood cells) when MRD was measured at pre-maintenance (83%, vs. 53%, p<0.0001) and post-maintenance (90% vs. 59%, p<0.0001). Importantly, the ability of MRD status to predict outcome (3-year PFS) held when analysis was restricted to just those patients who achieved a complete response as determined by conventional criteria (Pre-maintenance: 87% vs. 63%, p=0.0075; post-maintenance: 92% vs. 64%, p<0.0001).
The importance of using the most sensitive technique possible for MRD detection when evaluating response as a possible surrogate for outcome was shown by an analysis comparing Adaptive's NGS-based MRD test to seven-color flow cytometry with maximum sensitivity of one myeloma cell per 10,000 white blood cells. Of 163 patients MRD-negative by flow cytometry, 84 (51%) patients were positive using Adaptive's NGS-based test. Furthermore, there was a significant difference in 3-year PFS between flow-negative/NGS-MRD-negative and flow-negative/NGS-MRD-positive patients (Pre-maintenance: 86% vs. 66%, p=0.0002; Post-maintenance: 91% vs. 65%, p=0.0006).
"MRD-negativity is quickly replacing conventional complete response as the endpoint of choice when evaluating new medicines for myeloma in clinical trials," said Tom Willis, Ph.D., Senior Vice President and General Manager, Diagnostic Products, Adaptive Biotechnologies. "Multiple pharmaceutical companies are now using Adaptive's NGS-based MRD assessment method in their clinical trials due to its superiority over flow cytometry in terms of sensitivity, standardization and prediction of outcomes."
About Minimal Residual Disease
Minimal residual disease (MRD) refers to cancer cells that may remain in the body of a person with lymphoid cancer after treatment. These cells are present at levels undetectable by traditional microscopic examination (also called morphologic examination) of blood, bone marrow or a lymph node biopsy. Sensitive molecular technologies, such as the next-generation sequencing utilized by the Adaptive Biotechnologies clonoSEQ MRD Test, are needed for reliable detection of very low levels of MRD.
About the clonoSEQ® Process
The Adaptive Biotechnologies clonoSEQ Process enables physicians to utilize sequencing-based minimal residual disease (MRD) detection as an aid to clinical decision making for patients with lymphoid cancers (blood cancers). With its ability to detect cancer cells at a level as low as one per one million white blood cells, the clonoSEQ MRD Test is one to two orders of magnitude more sensitive than other methods of MRD detection, such as ASO-PCR and flow cytometry. The clonoSEQ Process was previously marketed as the ClonoSIGHT™ process by Sequenta, Inc., which was acquired by Adaptive Biotechnologies in January 2015.
MRD detection and quantification using the clonoSEQ Process involves two steps that are easily integrated into patient care. In the first step, the clonoSEQ ID Test, cancer cell DNA sequences are identified in a diagnostic sample. In the second step, the clonoSEQ MRD Test, follow-up samples are screened for the previously identified sequences in order to detect residual disease. ClonoSEQ test results are generated in seven days using the company's CLIA-certified, CAP-accredited laboratory. These results are provided to the ordering physician in a simple, actionable report that shows a patient's MRD status and level, as well as MRD trends over time via a secure online portal.