Adaptive Biotechnologies' clonoSEQ Minimal Residual Disease Test Predicts Relapse In Diffuse Large B-Cell Lymphoma Patients By Sensitively Detecting Circulating Tumor DNA

SEATTLE, April 1, 2015 /PRNewswire/ -- Adaptive Biotechnologies today announced publication of a study in TheLancet Oncology showing that analysis of circulating tumor DNA (ctDNA) using the company's next-generation sequencing-based minimal residual disease (MRD) detection and quantification technology (available clinically as the clonoSEQ MRD test) accurately identifies patients with diffuse large B-cell lymphoma (DLBCL) who are at risk of relapse after initial treatment, usually several months before disease can be detected via computed tomography (CT). The study, conducted with collaborators from the National Cancer Institute (NCI), suggests that the clonoSEQ MRD test may ultimately replace the imaging techniques currently used for DLBCL disease monitoring, which are imprecise and expose patients to radiation.

"Patients with DLBCL with low amounts of disease at relapse have better survival than those with more disease, which is the rationale for surveillance CT scans.  Because the ctDNA test detects disease at a molecular level, it detects microscopic disease, which cannot be detected by CT scans, and may improve patient survival," said Wyndham Wilson, MD, PhD, Chief, Lymphoma Therapeutics Section, NCI, senior author of the study. "Furthermore, ctDNA is non-invasive and can be employed as frequently as needed, unlike surveillance CT scans which expose patients to radiation and intravenous contrast."

The study included a total of 126 patients who had participated in clinical trials spanning from May 1993 to June 2013 and were followed for a median of 11 years post-treatment. To investigate whether ctDNA monitoring could overcome the limitations of standard imaging techniques, the researchers compared serial ctDNA samples to CT scans taken at the same time post-treatment in patients who had achieved complete remission ("surveillance monitoring"). The researchers also analyzed whether the presence of ctDNA at the beginning of the third cycle of treatment predicted relapse, regardless of whether patients achieved complete remission by the end of treatment ("interim monitoring").

The risk of relapse was more than 200 times greater in the 17/107 patients included in the surveillance monitoring analysis who developed detectable ctDNA post-remission (hazard ratio=228; 95 percent CI: 51-1022, p<0.0001). ctDNA predicted relapse with a positive predictive value of 88.2 percent (PPV; the probability that relapse will occur when ctDNA is detected) and a negative predictive value of 97.8 percent (NPV; the probability that relapse will not occur when ctDNA is not detected). Overall, the higher sensitivity of ctDNA surveillance resulted in a median lead time from ctDNA detection to relapse detected by CT of 3.5 months (0-200 months). In the 10 patients who relapsed late (>6 months post-treatment), the median lead time was 7.4 months (0-200).

Of the 108 patients included in the interim monitoring analysis, ctDNA was detected in 24 patients, 15 of whom eventually relapsed. Only 17 of the patients with undetectable interim ctDNA relapsed. Five years after the interim serum samples were taken, 80.2 percent (95 percent CI: 69.6-87.3 percent) of the patients who were negative for ctDNA were relapse-free, whereas only 41.7 percent (95 percent CI: 22.2-60.1 percent) of the positive patients were (p<0.0001). Detectable interim ctDNA had a PPV of 62.5 percent and an NPV of 79.8 percent. Fourteen out of the 15 patients with detectable ctDNA who relapsed did so within 6 months of the end of treatment, while only seven of the 17 without interim ctDNA who relapsed did so in this early time frame.

"Clinical use of the clonoSEQ MRD test to monitor DLBCL patients may provide earlier relapse detection, allowing the majority of patients who are cured following first-line treatment to avoid the radiation risk and cost of CT scans," said Tom Willis, PhD, Senior Vice President and General Manager, Diagnostics Products, Adaptive Biotechnologies. "DLBCL disease detection based on circulating tumor DNA using the clonoSEQ MRD test also has potential as a useful research biomarker for assessment of drug activity, early treatment intervention with targeted agents and monitoring of disease during maintenance treatment."

The study, "Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study," by Roschewski, et al., was published online ahead of print in TheLancet Oncology. DOI and web link: http://dx.doi.org/10.1016/S1470-2045(15)70106-3

About Diffuse Large B-Cell Lymphoma (DLBCL)
Lymphomas are blood cancers that develop in the lymphatic system. There are two main types of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). NHL mainly affects adults (95 percent of cases), with about half of patients diagnosed when they are over age 65. The American Cancer Society estimates that approximately 71,850 people will be diagnosed with NHL in 2015 and 19,790 will die from the disease. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL in the United States, accounting for about one third of all cases.

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. Very low levels of MRD can be reliably detected only by using sensitive molecular technologies, such as the next-generation sequencing utilized by Adaptive Biotechnologies' clonoSEQ MRD test.

About the clonoSEQ Process
Adaptive Biotechnologies' clonoSEQ process enables physicians to utilize sequencing-based minimal residual disease (MRD) detection as a clinical decision-making tool for patients with lymphoid cancers (blood cancers). Clinical validation studies have shown that this process offers significant improvements in sensitivity and performance over other MRD detection methods. 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 Adaptive Biotechnologies' 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.

About Adaptive Biotechnologies
Adaptive Biotechnologies Corporation is a platform-based, diagnostic-driven company that leverages NGS to profile T-Cell and B-Cell Receptors. This breakthrough enables in-depth characterization of the adaptive immune system, which is the primary defense against cancer. By incorporating immunosequencing into clinical care, Adaptive can enhance the diagnosis, prognosis and monitoring of cancer patients. For more information, please visit AdaptiveBiotech.com.

Media inquiries:
Sylvia Zaich
Adaptive Biotechnologies
650-243-3949
media@adaptivebiotech.com

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