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Can Clonal Diversity Complement MRD Assessment in Predicting Outcomes in Myeloma?

By: Celeste L. Dixon
Posted: Thursday, July 13, 2023

In a real-world setting, measurable residual disease (MRD) assessment has the same predictive power that has been seen in clinical trials, and assessment of clonal diversity may complement MRD assessment in predicting outcomes in patients with multiple myeloma, according to study results presented by Joaquin Martinez-Lopez, MD, PhD, of Complutense University, Madrid, and colleagues at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 8028). The study involved 482 patients at the University of California, San Francisco: 304 were newly diagnosed, and 178 were receiving second-line treatment.

At the heart of the investigators’ research was the observation that some patients with nondetectable MRD relapses, whereas some patients who achieved MRD positivity, even those followed for years, did not relapse. They sought to assess MRD by next-generation sequencing of immunoglobulin genes and the long-term impact of depth of response as well as clonal diversity—defined as the number of unique immunoglobulin (IgH, IgK, or IgL) sequences in each sample—on clinical outcome.

Both MRD-positive and -negative patients who had not relapsed had higher clonal diversity than their MRD-positive and -negative counterparts who had relapsed. “This was also observed independently for the three receptors analyzed (IgH, P = .026; IgK, P = .036; and IgL, P = .036),” wrote Dr. Martinez-Lopez and co-researchers. Further, “patients with more than 66,000 IgH unique sequences at the time of maximum response had a prolonged progression-free survival.”

Overall, the team analyzed 1,098 samples for MRD, with a median follow-up of 26 months. Of the 482 patients, 38% achieved MRD negativity (< 10-6) on one or more samples; clonal diversity was available for 87 of these patients. In the newly diagnosed group, 39% achieved MRD negativity at the level of 10-6 at least once, and they had a prolonged progression-free survival versus patients who were persistently MRD-positive (P > .0001). Of the 178 patients who received therapy for relapsed disease, 64 achieved MRD negativity at 10-6 (36%), and their progression-free survival was also prolonged versus patients who remained MRD-positive (P = .03).

Disclosure: The study authors’ disclosure information can be found at

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