Where MRD Testing Fits Into Myeloma’s Treatment and Regulatory Landscape

In an interview with CancerNetwork® at the 23rd Annual International Myeloma Society (IMS) Meeting & Exposition, C. Ola Landgren, MD, PhD, discussed where minimal residual disease (MRD) testing fits into current treatment landscape conversations with regulators and payers in multiple myeloma.

Landgren traced his own work on this question back over 2 decades, including an evidence meta-analysis developed during his time at the National Cancer Institute’s intramural program, which contributed to a 2024 presentation before the FDA’s Oncologic Drugs Advisory Committee (ODAC). ODAC voted unanimously in favor of MRD as an acceptable early endpoint for accelerated drug approval.¹ Landgren noted that iberdomide (Zenbexus) became the first new drug application submitted to the FDA using MRD as a primary end point, ultimately receiving approval based on an MRD negativity benefit over the control arm.^2,3 Beyond its regulatory role, Landgren pointed to the phase 3 MIDAS study (NCT04934475) as evidence that MRD-negative status can also guide individualized treatment decisions, such as foregoing transplantation.⁴ He closed by noting that current MRD testing still relies on bone marrow sampling, and that the development of blood-based MRD tests, now underway at several companies, represents the next major step for the field.

Landgren is a professor, chief of the Division of Myeloma in the Department of Medicine, director of the Sylvester Myeloma Institute, co-leader of the Translational and Clinical Oncology Program, and Paul J. DiMare Endowed Chair in Immunotherapy at the University of Miami Miller School of Medicine. He is also an editorial advisory board member of the journal ONCOLOGY®.

Transcript:

CancerNetwork: Where does MRD testing fit into today’s current treatment landscape conversations with regulators and payers? Is the field at a point to use it to guide real-time treatment decisions?

MRD negativity is very important in multiple myeloma. I worked on it for over 20 years. I spent a decade working at the intramural program at the NCI outside Washington, DC, in Bethesda, and I started the work that led to the evidence meta-analysis, which was subsequently followed up by other groups, including the i2 team and others. This eventually led to presentations at ODAC, the Oncologic Drugs Advisory Committee, in 2024, where we presented the evidence meta-analysis, and the i2 program presented their data there as well. ODAC voted 12 to 0 in favor of MRD being an acceptable early end point for accelerated drug approval. This is a huge step forward. In early 2026, the FDA updated its guidance document on MRD as a tool for an early end point for accelerated approval in [multiple] myeloma. Multiple myeloma now has a tool that none of the other malignancies have, so we can develop drugs much faster, which was the whole idea of moving this forward for all these years.

We don’t have to discuss whether MRD is an important tool from a regulatory perspective anymore; in fact, it is now an endorsed end point by the FDA, and we saw in 2026, when iberdomide was the first new drug application, or NDA, submitted to the FDA with MRD as one of the primary end points. You can have more than one end point, and if you meet one of them, you can submit your data. Iberdomide was FDA approved based on MRD [negativity] being roughly twice as high for iberdomide vs the control arm. This is a huge step forward.

The next question that’s now being asked, and it’s been asked for several years, is: could MRD also be used to differentiate treatment? I think there’s a lot of data supporting that. The MIDAS study, published in the New England Journal of Medicine this past year, shows that for patients who are MRD negative, you can forego transplantation. In fact, patients with standard risk who are MRD negative, whether they were transplanted or treated with combination therapy, showed no difference in outcomes with the current follow-up time. I think we will see more and more use of MRD to potentially forego different steps, in this case, transplantation. You could also use it to de-escalate combination therapy down to more of a maintenance therapy, maybe even stop treatment in some patients, and you could also use it to reactivate [treatment]. The phase 3 PERSEUS study [NCT03710603] reactivated the use of daratumumab [Darzalex] in addition to lenalidomide [Revlimid] maintenance; patients who were MRD negative and turned positive were put back on combination therapy in that trial.⁵ MRD is not only for regulatory purposes, but for [treating] patients, and this is really individualized care where I think MRD will play a role.

The last piece I think is important to emphasize is that MRD testing is still based on bone marrow. What needs to happen next is to have blood-based MRD tests, and there are a lot of companies working on this. That will really change the field for the better for patients.

References

1. April 12, 2024 Meeting of the Oncologic Drugs Advisory Committee (ODAC). Streamed live April 12, 2024. Accessed September 25, 2026. https://tinyurl.com/2tbe3f4k
2. U.S. Food and Drug Administration accepts Bristol Myers Squibb’s new drug application for iberdomide in patients with relapsed or refractory multiple myeloma. News release. Bristol Myers Squibb. February 17, 2026. Accessed September 25, 2026. https://tinyurl.com/4c8mb6ex
3. FDA grants accelerated approval to iberdomide with daratumumab and hyaluronidase-fihj and dexamethasone for multiple myeloma. News release. August 13, 2026. Accessed September 25, 2026. https://tinyurl.com/38258auk
4. Perrot A, Lambert J, Hulin C, et al. Measurable residual disease-guided therapy in newly diagnosed myeloma. N Engl J Med. 2025;393(5):425-437. doi:10.1056/NEJMoa2505133
5. Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2024;390(4):301-313. doi:10.1056/NEJMoa2312054