Next-Generation Sequencing Minimal Residual Disease Testing in Blood Cancer Is Needed Now More Than Ever

The treatment landscape for blood cancers continues to evolve bringing new innovative medicines, such as immunotherapy, adoptive cell therapy, and others, to patients. With these advances, it’s just as important that clinicians have new approaches to evaluate just how well those treatments are working.

Minimal residual disease (MRD) testing, which is used in clinical trials to assess efficacy in potential new medicines, is also being used to guide day-to-day management of patient treatment for blood cancers such as multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and B-cell acute lymphoblastic leukemia (B-ALL). MRD describes the small number of cancer cells that remain in the body following treatment. An MRD positive test result means that disease was still detected after treatment, while an MRD negative result means no disease was detected after treatment. MRD tests provide an opportunity to potentially detect disease before it progresses and offers timely information for both physicians and patients about how a treatment is working at different points in a patient’s treatment journey.

Adaptive’s clonoSEQ®Assay, for example, is the first and only FDA-cleared assay that measures MRD in blood or bone marrow samples from patients with CLL and bone marrow samples from patients with MM and B-ALL. The FDA clearance validates the high performance and reproducibility of the assay.¹ Powered by next-generation sequencing (NGS), clonoSEQ can identify millions of unique B-cell and T-cell receptors from a single sample and with a high specificity, enables identification and tracking of individual cancer cells.^2,3 This allows for an accurate MRD result, enabling clinicians to get a clear picture of what is happening with a patient’s disease, helping to predict outcomes, assess response, monitor remission, and detect potential relapse.¹ In fact, in studies, clonoSEQ identified additional MRD-positive patients who were MRD-negative by flow cytometry.^{4, 5, 6, 7}

When doctors are able to get more precise information about a patient’s disease status or clinical insight into how that patient is responding to treatment, they can better predict what mayhappen as they consider the treatment options. The value of MRD as a critical measure of outcomes in patients with blood cancers is supported by an ever-growing body of clinical evidence and real-world data, which is even more important now as newer drugs make deeper responses and longer-lasting remissions possible. One abstract for example, presented at last year’s American Society of Hematology (ASH) conference suggested that when a clinical decision was made to change therapy based on MRDresults, patients had a prolonged progression free survival (PFS) compared to those in which therapy remained the same.⁸

Let’s also look at it from a patient perspective. What is often of top importance for patients being treated with blood cancers is whether they are responding to therapy or in jeopardy of relapsing. For patients in remission, periodic MRD testing can help provide peace of mind that their disease is under control or give an indication that their disease is returning, empowering them to work with their physician on an action plan.

And when I think about the full power of clonoSEQ, which looks at the cancer itself and doesn’t rely on response criteria, I also think about what it means for the ability of a clinician to help a patient manage the costs of some of these new treatments.

For a patient that has gone into remission, the level of detail physicians can get with clonoSEQ may help a patient avoid the financial and physical impact of treatments that may, at least for a time, not be needed. In fact, another abstract presented at the ASH 2020 conference – which was based off a theoretical model – showed that using clonoSEQ to make treatment decisions could lead to improved patient outcomes and reduce overall cost.⁹

When it comes to reimbursement, Medicare already covers clonoSEQ for blood cancer patients with CLL, MM and B-ALL in the United States, meaning patients on Medicare have no out-of-pocket costs for the test. The Adaptive Assist Patient Support Program is also available to help patients understand the billing process and potential out-of-pocket costs, assist with prior authorizations for all incoming clinical orders, appeal for the maximum benefits and lowest out-of-pocket cost and help eligible patients with out-of-pocket costs after coverage.

Every person’s cancer journey is different and that is why it is important to have a highly sensitive and precise monitoring tool that gives physicians and patients insights that will allow them to have informed and robust conversations on treatment approaches.

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Lance Baldo, MD

Chief Medical Officer

Dr. Lance Baldo, MD, has served as Adaptive’s Chief Medical Officer since May 2019. From February 2010 to April 2019, Lance served in various roles of ascending responsibility with the Roche Group and its affiliates, including most recently as Senior Vice President and Head of U.S. Medical Affairs of Genentech. Prior to joining the Roche Group, Lance served as Vice President, Global Medical Science and Affairs at The Medicines Company, a public biopharmaceuticals company, from September 2005 to February 2010. Lance holds an MD from the University of Connecticut School of Medicine and a BA in Biology from Johns Hopkins University.

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About clonoSEQ

clonoSEQ® is available as an FDA-cleared in vitro diagnostic (IVD) test service provided by Adaptive Biotechnologies to detect minimal residual disease (MRD) in bone marrow from patients with multiple myeloma or B-cell acute lymphoblastic leukemia (B-ALL) and blood or bone marrow from patients with chronic lymphocytic leukemia (CLL). clonoSEQ is also available for use in other lymphoid cancers and specimen types as a CLIA-validated laboratory developed test (LDT). For important

information about the FDA-cleared uses of clonoSEQ including test limitations, please visit clonoSEQ.com/technical-summary.

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About Adaptive Biotechnologies

Adaptive Biotechnologies is a commercial-stage biotechnology company focused on harnessing the inherent biology of the adaptive immune system to transform the diagnosis and treatment of disease. Adaptive’s proprietary immune medicine platform reveals and translates the massive genetics of the adaptive immune system with scale, precision and speed to develop products in life sciences research, clinical diagnostics and drug discovery.

1. clonoSEQ®. [technical summary]. Seattle, WA: Adaptive Biotechnologies Corporation; 2020.
2. Ching T, et al. BMC Cancer. 2020;20:612.
3. Carlson CS, et al. Nat Commun. 2013;4:2680.
4. Wood B, et al. Blood. 2018; 131(12):1350-1359.
5. Perrot A, et al. Blood. 2018;132(23):2456-2464.
6. Wu D, et al. Clin Cancer Res. 2014;20(17):4540-8.
7. Martinez-Lopez J, et al. Blood Adv. 2020;4(14):3295-3301.
8. Martinez-Lopez JM, et al. Abstract #2237. Presented at: the 62nd ASH Annual Meeting and Exposition. December 6, 2020.
9. Carlson JJ, et al. Abstract 3426. Presented at: the 62nd ASH Annual Meeting and Exposition; December 2-10, 2020.