Myeloma Guidelines Call for Yearly Measurable Residual Disease Testing

The National Comprehensive Cancer Network (NCCN) has updated its guidelines for multiple myeloma, strengthening recommendations for measurable residual disease (MRD) testing and adding a dedicated section explaining when and how the testing should be used.

The updates, included in Version 1.2027 of the guidelines, expand MRD testing across different points in treatment, including once a year for patients receiving maintenance therapy.

MRD testing looks for very small numbers of cancer cells that can remain after treatment and may not be detected by standard tests. The guidelines now prefer tests with a sensitivity of 10⁻⁶, meaning they can detect approximately one cancer cell among 1 million cells. A sensitivity of 10⁻⁵, or approximately one cancer cell among 100,000 cells, is listed as the minimum recommended level.

For patients, the changes may provide another way for their care teams to follow how deeply the cancer has responded to treatment and how that response changes over time.

What do the updated NCCN guidelines recommend for MRD testing in multiple myeloma?

For the first time, the NCCN multiple myeloma guidelines include a dedicated page, called MYEL-E, that brings together recommendations for MRD testing.

The guidelines recommend bone marrow-based MRD testing using either next-generation sequencing (NGS) or multicolor flow cytometry. NGS looks for cancer-associated DNA sequences that can be tracked after treatment, while flow cytometry identifies abnormal cells based on characteristics detected in the laboratory.

Recommended testing timepoints have also expanded to include annual testing during maintenance therapy and testing after later lines of treatment, including after chimeric antigen receptor (CAR)-T cell therapy, which uses a patient's own immune cells to recognize and attack cancer.

The changes place greater emphasis on following MRD over time rather than relying on a single result.

Research has linked MRD negativity, meaning cancer is not detected at the test's level of sensitivity, with better outcomes in multiple myeloma. A large meta-analysis published in Blood Advances found that MRD negativity was associated with longer progression-free survival, or the time patients lived without their disease worsening, and overall survival.

How can MRD results affect multiple myeloma treatment decisions?

MRD results may also provide clinicians with additional information when making treatment decisions with their patients.

According to the guideline update, MRD negativity and sustained MRD negativity across repeated tests can be considered when making decisions about continuing, increasing or decreasing treatment. Rising MRD positivity may warrant closer monitoring and clinical evaluation.

"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," Dr. Ola Landgren said in the news release announcing the update.

He also emphasized the importance of following MRD over time, noting that sustained MRD negativity can provide more information than a single negative result.

"Sustained MRD negativity is more informative than a single negative result," he said.

Researchers are also studying whether sustained MRD negativity could eventually help identify some patients who may be able to stop maintenance therapy. However, MRD-guided treatment discontinuation remains under investigation and should be considered alongside a patient's overall disease and treatment history.

How is MRD testing for multiple myeloma performed?

MRD testing for multiple myeloma is performed using a bone marrow sample. Under the updated recommendations, the sample can be analyzed using NGS or multicolor flow cytometry.

The guidelines specifically reference clonoSEQ, an NGS assay made by Adaptive Biotechnologies. The test is FDA-cleared for detecting and monitoring MRD in bone marrow from patients with multiple myeloma and can reach a sensitivity of 10⁻⁶ when sufficient sample material is available.

The guideline update was announced Sept. 17 in a news release from Adaptive Biotechnologies, the company that makes clonoSEQ.

Although patients may not have direct access to the full professional NCCN guidelines, their oncology care teams can use the recommendations when making decisions about monitoring and treatment. Patients can ask their care team whether MRD testing is appropriate for them, how sensitive the test being used is and whether testing will be repeated during treatment.

References

1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. Version 1.2027.
2. Adaptive Biotechnologies. "Adaptive Biotechnologies Announces Update to NCCN Guidelines for Multiple Myeloma, Strengthening MRD Testing Recommendations and Specifically Referencing clonoSEQ." Published Sept. 17, 2026.
3. Munshi NC, et al. "A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma." Blood Advances. 2020;4(23):5988-5999.
4. Ntanasis-Stathopoulos I, et al. "Evaluating Minimal Residual Disease Negativity as a Surrogate Endpoint for Treatment Efficacy in Multiple Myeloma: A Meta-Analysis of Randomized Controlled Trials." American Journal of Hematology. 2025.
5. Derman BA, et al. "Discontinuation of maintenance therapy in multiple myeloma guided by multimodal measurable residual disease negativity (MRD2STOP)." Blood Cancer Journal. 2024;14:170.

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