Adaptive Biotechnologies Corporation (Nasdaq: ADPT) has announced the launch of an enhanced version of its clonoSEQ assay for measurable residual disease (MRD) detection in diffuse large B-cell lymphoma (DLBCL). The upgraded assay, which utilizes circulating tumor DNA (ctDNA), delivers a significant 7-fold increase in sensitivity compared to previous versions.
The Seattle-based commercial stage biotechnology company revealed that the enhanced assay incorporates an optimized DNA extraction methodology and maximizes sample input while maintaining the same proprietary technology that detects MRD by reading the full immune receptor sequence of malignant B cells rather than relying on individual point mutations.
"The enhancements to our clonoSEQ ctDNA-based DLBCL test offering strengthen the assay's already-deep clinical sensitivity without compromising our unparalleled specificity," said Susan Bobulsky, chief commercial officer of MRD at Adaptive Biotechnologies. "The assay's strong performance on both fronts makes it possible to deliver accurate, actionable insights in the clinic and empowers drug developers to precisely target treatment intensification strategies for patients who remain MRD-positive at end of frontline therapy while minimizing the risk of overtreatment."
Regulatory Approval and Clinical Validation
The enhanced clonoSEQ assay has received approval from the New York State Department of Health Clinical Laboratory Evaluation Program (CLEP) for the detection and monitoring of MRD in patients with DLBCL. This approval coincides with the updated National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for B-Cell Lymphomas, which now recommend ctDNA testing for MRD assessment in patients with PET-positive DLBCL at the end of first-line treatment.
The assay was previously made available for research use in November 2023 and has already been incorporated into both biopharma-sponsored and investigator-initiated prospective trials. Data presented at ASH 2024 by Bond and colleagues demonstrated that MRD negativity post-cycle six, as assessed by clonoSEQ, was highly prognostic of progression-free survival.
Clinical Impact and Market Position
clonoSEQ stands as the first and only DLBCL MRD test available for clinical use. Since securing Medicare coverage for DLBCL in July 2022, Adaptive has provided MRD testing for more than 2,800 DLBCL patients, with the test being used to manage and inform patient care by over 640 providers in 2024 alone.
The clinical significance of this enhanced assay is substantial given the prevalence and relapse patterns of DLBCL. As the most common form of non-Hodgkin lymphoma (NHL), DLBCL accounts for approximately one-third of NHL patients in the United States, with more than 18,000 new diagnoses annually. About 30-40% of patients experience relapse, most within the first two years after treatment.
Importance of MRD Testing in DLBCL Management
DLBCL outcomes can vary widely following frontline treatment, making accurate risk stratification through MRD testing critical for clinical decision-making. The clonoSEQ assay helps clinicians differentiate between a likely cure and an impending relapse, enabling more personalized treatment approaches.
MRD testing provides several clinical benefits, including:
- Assessment of treatment response
- Early detection of cancer recurrence
- Guidance for treatment plan adjustments
- Risk stratification of patients
As clinical trials exploring novel MRD-directed treatment consolidation strategies to reduce relapse rates continue to grow, the role for highly sensitive and specific ctDNA-based tests like clonoSEQ is expected to expand.
Technical Capabilities of clonoSEQ
The clonoSEQ assay is the first and only FDA-cleared in vitro diagnostic test service to detect minimal residual disease in bone marrow from patients with multiple myeloma or B-cell acute lymphoblastic leukemia, and in blood or bone marrow from patients with chronic lymphocytic leukemia. For DLBCL patients, clonoSEQ testing is currently available as a laboratory-developed test performed at Adaptive's CLIA-certified lab in Seattle.
The assay leverages Adaptive Biotechnologies' proprietary immune medicine platform to identify and quantify specific DNA sequences found in malignant cells. This allows clinicians to assess and monitor MRD during and after treatment, providing standardized, accurate, and sensitive measurement that helps physicians predict patient outcomes, assess treatment response, inform therapy changes, monitor disease burden, and detect potential relapse early.
Broader Applications and Company Vision
Adaptive Biotechnologies focuses on harnessing the inherent biology of the adaptive immune system to transform disease diagnosis and treatment. The company's proprietary immune medicine platform reveals and translates the genetics of the adaptive immune system with scale, precision, and speed.
Beyond DLBCL, clinical outcomes have been shown to be strongly associated with MRD levels measured by clonoSEQ in patients diagnosed with chronic lymphocytic leukemia, multiple myeloma, and B-cell acute lymphoblastic leukemia. The company's goal is to develop and commercialize immune-driven clinical products tailored to each individual patient, potentially revolutionizing the approach to cancer and autoimmune disorders.
