Children's Oncology Group/Pediatric Blood and Marrow Transplant Consortium Study Shows Adaptive Biotechnologies' clonoSEQ® Minimal Residual Disease (MRD) Test Superior to Flow Cytometry in Predicting Post-Transplant Relapse and Survival in Acute Lymphoblastic Leukemia

SEATTLE, June 4, 2015 /PRNewswire/ -- Adaptive Biotechnologies announced the publication of a joint study with the Children's Oncology Group (COG) and Pediatric Blood and Marrow Transplant Consortium (PBMTC) demonstrating that minimal residual disease detected using next-generation sequencing (NGS), available clinically as the clonoSEQ^® MRD Test through the company's CLIA-certified laboratory, can more accurately predict relapse and survival compared to multichannel (6-color) flow cytometry in pediatric acute lymphoblastic leukemia (ALL) patients undergoing donor stem cell transplants.

"The increased sensitivity of next-generation sequencing-based MRD detection allowed identification of patients at significant risk of relapse who would otherwise be defined as MRD-negative with flow cytometry and therefore thought to be at low risk," said Michael Pulsipher, MD, Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute/University of Utah School of Medicine, and lead author of the study. "Pre-transplant, NGS-based MRD detection defined good risk patients who could potentially be eligible for less intense treatment approaches, while post-transplant this sensitive method identified MRD-positive patients who may benefit from interventions aimed at preventing relapse."

Analysis of pre-transplant bone marrow samples from 40 pediatric patients with B-cell ALL found that NGS-based MRD detection predicted relapse and overall survival (OS) significantly better than flow cytometry (p<0.0001 and p=0.003, respectively). The two-year relapse probabilities were 53 percent and 0 percent among NGS-MRD-positive and -negative patients, respectively (p<0.0001), compared to 46 percent and 16 percent among flow MRD-positive and -negative patients (p=0.02). The two-year survival probabilities in MRD-negative patients were 96 percent and 77 percent for NGS and flow cytometry, respectively (p=0.003).

In the post-transplant setting, NGS-MRD detection was also better at predicting relapse than flow cytometry, especially when applied to samples taken early after transplant. One month post-transplant, results from MRD analysis using flow cytometry were not able to discriminate between patients who ultimately relapsed and those who did not, whereas MRD analysis using the NGS-based method showed an estimated relapse probability of 67 percent in positive patients vs. 25 percent in negative patients (p=0.01). The better predictive power of NGS-based MRD detection vs. flow cytometry held at day 100 and 8 months post-transplant. MRD as detected at any point post-transplant using the NGS-based method led to an increase in relapse (hazard ratio: 7.7; p=0.05), independent of other factors.

"This research establishes the potential of next-generation sequencing-based MRD detection in stratifying pediatric ALL patient treatment based on risk of relapse," said Tom Willis, PhD, Senior Vice President and General Manager, Diagnostic Products, Adaptive Biotechnologies. "Physicians are already using the clonoSEQ Process in the clinical management of their patients with ALL and other lymphoid cancers."

The study, "IgH-V(D)J NGS-MRD measurement pre- and early post- allo-transplant defines very low and very high risk ALL patients", by Pulsipher, et al., was published in the May 28 issue of Blood.

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.

About Adaptive Biotechnologies^®
Adaptive Biotechnologies is the pioneer and leader in combining high-throughput sequencing and expert bioinformatics to profile T-cell and B-cell receptors. Adaptive is bringing the accuracy and sensitivity of its immunosequencing platform into laboratories around the world to drive groundbreaking research in cancer and other immune-mediated diseases. Adaptive also translates immunosequencing discoveries into clinical diagnostics and therapeutic development to improve patient care.

About the Children's Oncology Group
The Children's Oncology Group (COG) is the world's largest organization devoted exclusively to childhood and adolescent cancer research. The COG unites more than 9,000 experts in childhood cancer at more than 200 leading children's hospitals, universities, and cancer centers across North America, Australia, New Zealand, and Europe in the fight against childhood cancer. Today, more than 90 percent of 14,000 children and adolescents diagnosed with cancer each year in the United States are cared for at COG member institutions. COG is part of the NCI's National Clinical Trials Network (NCTN) and is supported primarily through NCI research grant funding. For more information, please visit http://www.childrensoncologygroup.org.

About the Pediatric Blood and Marrow Transplant Consortium
The Pediatric Blood and Marrow Transplant Consortium is the largest consortium dedicated to research and advocacy for blood and marrow transplantation and cellular therapy studies in the world.  Over 80 centers from North America, Australia and New Zealand are full members, with affiliate members throughout the world.  The PBMTC is supported through grants from the National Cancer Institute, the National Heart, Lung and Blood Institute, the National Institute of Allergy and Infectious Diseases, and the St. Baldrick's Foundation.  For more information, please visit www.pbmtc.org.

Research reported in this press release was supported by the Children's Oncology Group, the National Cancer Institute of the National Institutes of Health under award numbers U10CA180886; U10CA180899; U10CA098543; and U10CA098413. COG activities were supported by R01CA1116660.  PBMTC activities were supported by 2U01HL069254 and a consortium grant from the St. Baldrick's Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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SOURCE Adaptive Biotechnologies