ClonoSeq ctDNA-based MRD Assay Launched for Patients With DLBCL

The clonoSEQ® assay has been launched as a diagnostic tool for minimal residual disease (MRD) assessment in patients with diffuse large B-cell lymphoma (DLBCL), according to a press release from Adaptive Biotechnologies Corporation.¹

The assay, which uses circulating tumor DNA (ctDNA) in the bloodstream to measure tumor burden, has been shown to have prognostic value in predicting disease relapse in hematologic malignancies. In addition to being available as a laboratory-developed test (LDT), clonoSEQ assay will now be accept blood samples in Streck® tubes, which will expand access to the assay to more patients.

“We are excited to continue to expand access to clonoSEQ as a highly specific and less invasive tool for DLBCL monitoring, which will complement the current standard imaging methods,” Nitin Sood, MS, chief commercial officer for MRD at Adaptive Biotechnologies, said in a statement. “By measuring ctDNA in blood, clonoSEQ provides clinicians with a sensitive and quantitative assessment of disease burden so that they can detect relapse sooner and are better equipped to create a more precise treatment plan for each patient.”

clonoSEQ is the only MRD test that is covered by Medicare for all patients with DLBCL regardless of the treatment regimen they have received, the number of lines of therapy, or the testing timepoint.

clonoSEQ is available as an FDA-cleared in vitro diagnostic performed at a site in Seattle, Washington. It uses multiplex polymerase chain reaction (PCR) and next-generation sequencing (NGS) to identify certain DNA sequences from malignant cells in bone marrow from patients with multiple myeloma or B-cell acute lymphoblastic leukemia (ALL) and blood or bone marrow from patients with chronic lymphocytic leukemia (CLL), as well as the Clinical Laboratory Improvement Amendments–validated LDT for blood in DLBCL.

MRD status is recognized as predictive of clinical outcomes and response to therapy in patients with multiple myeloma, ALL, CLL, and DLBCL. Imaging by PET and/or CT scan is standard for detecting disease progression in patients with these diseases, but results can be inconclusive or not visible until later.

In DLBCL, ctDNA has been shown to identify risk of recurrence at a median of 3.5 months before clinical evidence from CT scans.² It has a role in patients at risk of recurrence following frontline treatment and after autologous stem cell transplant. It has also been shown to be effective in predicting relapse at or before radiographical confirmation in 29 out of 30 patients who have received axicabtagene ciloleucel (axi-cel; Yescarta) chimeric antigen receptor T-cell therapy for DLBCL, whereas all patients with a durable response to axi-cel had undetectable ctDNA at or before 3 months from infusion.³ Prediction of early relapse or durable remission based on MRD can help optimize treatment decisions for physicians that will improve outcomes for patients.

“The continued development of new treatments for DLBCL requires novel, precise ways to monitor disease progression. Imaging is an important monitoring tool but also has known clinical limitations and drawbacks for patients,” Tara Graff, DO, a hematologist/oncologist at Mission Cancer + Blood in Des Moines, Iowa who has served a principal investigator of multiple lymphoma clinical trials, said in a press release.¹ “clonoSEQ testing in blood can serve as a complement to imaging, aiding in my work-up and decision-making process for [patients with] DLBCL and in some cases, helping spare patients from unnecessary procedures and treatments.”

_References:

_{1. Adaptive Biotechnologies announces launch of clonoSEQ® to assess minimal residual disease (MRD) in patients with diffuse large B-cell lymphoma (DLBCL) using circulating tumor DNA (ctDNA). Adaptive Biotechnologies. December 1, 2022. Accessed December 5, 2022. https://yhoo.it/3UzlMdl}

_{2. Roschewski M, Dunleavy K, Pittaluga S, et al. Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study. Lancet Oncol. 2015;16(5):541-549. doi:10.1016/S1470-2045(15)70106-3}

_{3. Frank MJ, Hossain NM, Bukhari A, et al. Monitoring of circulating tumor DNA improves early relapse detection after axicabtagene ciloleucel infusion in large B-cell lymphoma: results of a prospective multi-institutional trial. J Clin Oncol. 2021;39(27):3034-3043. doi:10.1200/JCO.21.00377}