MRD May Be Useful for Guiding Treatment Decisions in Multiple Myeloma

Although it’s widely agreed upon that measurable residual disease (MRD) is a useful prognostic marker in multiple myeloma (MM), the utility of MRD-guided treatment decisions is less understood. New research, however, points to a potential benefit of using MRD to guide these decisions.

The retrospective study, published recently in Journal of Hematology & Oncology, analyzed the outcomes of 400 patients with MM, a group of which had treatment decisions based on their MRD status. The patients with MRD-guided treatment decisions had superior progression-free survival (PFS): 104 vs 62 months.

According to the researchers, the findings have important implications for expanding the use of MRD in MM.

“Depth of MRD is commonly considered the best prognostic factor in MM, and a good surrogate marker for survival in clinical trials,” wrote the researchers. “However, some myeloma experts question the employment of MRD to guide MM treatment due to the lack of evidence. Our results suggest that the use of MRD to make clinical decisions has a positive impact on survival outcomes.”

The researchers note that the potential of using MRD for guiding treatment decisions will need to be validated in prospective, randomized clinical trials.

All patients included in the study had extensive MRD monitoring while undergoing frontline therapy. Sixty-seven of these patients had treatment decisions made based on their MRD results, typically during maintenance treatment. For the 33 patients who were MRD negative, treatment was reduced for 3 and discontinued for 30. Changes in treatment were made for the 34 MRD-positive patients, 27 of whom received intensified treatment and 7 received a new treatment.

Overall, while undergoing maintenance, PFS did not differ among patients reaching MRD-negative status at least once whether therapy was stopped (n = 24) or continued (n = 162). For those who became MRD positive during maintenance, however, either changing therapy or intensifying it (n = 43) vs not adjusting treatment (n = 171) did increase PFS: 39 months vs NA, respectively.

“Interestingly, PFS improved when treatment was modified in patients who were MRD positive; while PFS was not different according to the discontinuation or persistence of therapy when MRD negativity was achieved,” wrote the researchers.

In a multivariate analysis of factors like age, sex, myeloma isotype, and hemoglobin, results showed that just MRD and age had a significant impact for making clinical decisions.

Notably, the approach used to measure MRD did not seem to sway results. There were no significant differences when MRD was determined using flow cytometry or next-generation sequencing.

“We found that MRD is useful in guiding clinical decisions during initial therapy and has a positive impact on PFS in MM patients,” tha authors concluded. “This potentially opens a new dimension for the use of MRD in MM, but this role still remains to be confirmed in prospective, randomized clinical trials.”

Reference

Martinez-Lopez J, Alonso R, Wong S, et al. Making clinical decisions based on measurable residual disease improves the outcome in multiple myeloma. J Hematol Oncol. Published online August 17, 2021. doi:10.1186/s13045-021-01135-w