NCCN Guidelines Strengthen MRD Testing Recommendations in Multiple Myeloma

The NCCN has updated its Clinical Practice Guidelines in Oncology for multiple myeloma to strengthen recommendations for minimal residual disease (MRD) testing, including a dedicated page outlining Principles of MRD Testing, according to a news release from Adaptive Biotechnologies.¹ The update establishes a sensitivity of 10⁻⁶ as preferred for MRD assessment and names the clonoSEQ^® assay as an FDA-cleared next-generation sequencing (NGS) test for this purpose.

What do the updated NCCN MRD testing recommendations include?

For the first time, the guidelines (version 1.2027) include a dedicated page, MYEL-E, that consolidates the Principles of MRD Testing to give clinicians a more consistent approach to using MRD testing.² Bone marrow–based MRD can be assessed using NGS with an FDA-approved assay, such as clonoSEQ, or by multicolor flow cytometry; clonoSEQ is the only assay specifically named in the guidelines.

The minimum recommended sensitivity for MRD testing is 10⁻⁵, with 10⁻⁶ preferred when possible because it carries higher prognostic value. The recommended timepoints for MRD assessment were expanded to include a baseline sample at diagnosis or before treatment to identify the dominant clonotype for NGS, after induction therapy, after hematopoietic cell transplant or CAR T-cell therapy, at the time of relapse or a substantive treatment change, and at regular intervals during maintenance or surveillance, with annual assessment serving as a general recommendation.

How can MRD testing guide treatment decisions?

The updated guidelines note that MRD negativity and sustained MRD negativity can help guide treatment escalation, de-escalation, and maintenance therapy as part of shared decision-making with patients. On the other hand, rising MRD positivity may prompt, at a minimum, closer monitoring and clinical evaluation. The framework builds on evidence that MRD negativity correlates with longer progression-free survival (PFS) and overall survival, with sustained MRD negativity for 12 months or longer carrying a strong correlation with prolonged PFS.

“Greater sensitivity matters, as it is associated with clinical outcomes, and assessing MRD at a sensitivity of 10⁻⁶ gives us a more precise understanding of the depth of response,” said Ola Landgren, MD, PhD, director of the Sylvester Myeloma Institute at Sylvester Comprehensive Cancer Center and the University of Miami Miller School of Medicine, in the news release.¹ “Incorporating MRD into decisions about treatment duration, including the possibility of discontinuing therapy in selected patients with sustained MRD negativity, moves the field toward a more individualized approach in which we aim not only to achieve deep responses, but also to avoid unnecessary treatment.”

What is clonoSEQ?

clonoSEQ is the first and only FDA-cleared in vitro diagnostic test for detecting and tracking MRD in patients with multiple myeloma or B-cell acute lymphoblastic leukemia using bone marrow, and in patients with chronic lymphocytic leukemia using blood or bone marrow. The assay identifies and quantifies DNA sequences in malignant cells to detecting one cancer cell in 1 million healthy cells, thereby assisting clinicians to assess and monitor MRD over time. The test has been studied in more than 300 peer-reviewed publications. NGS-based MRD testing with an FDA-approved assay has been recognized as a surrogate end point for accelerated drug approvals in multiple myeloma.

Why do the updated guidelines matter?

By consolidating MRD testing recommendations in one place, the updated guidelines may support more informed conversations between patients and care teams about disease status, treatment decisions, and ongoing monitoring.

“The updated myeloma guidelines provide more detailed recommendations for MRD testing timepoints and frequency, helping clinicians incorporate MRD assessment into care throughout the myeloma treatment continuum,” Susan Bobulsky, chief commercial officer of MRD at Adaptive Biotechnologies, concluded in the news release.¹

References

1. Adaptive Biotechnologies announces update to NCCN Guidelines for multiple myeloma, strengthening MRD testing recommendations and specifically referencing clonoSEQ. News release. Adaptive Biotechnologies Corporation. September 17, 2026. Accessed September 18, 2026. https://tinyurl.com/mr4xrznm
2. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Multiple Myeloma. Version 1.2027. National Comprehensive Cancer Network. September 9, 2026. Accessed September 18, 2026. https://tinyurl.com/47x35wch