Minimal residual disease negativity following treatment for newly diagnosed multiple myeloma is associated with long-term survival, according to findings from a meta-analysis of relevant data.
The findings suggest that assessment for minimal residual disease (MRD) should be included as an end point in clinical trials of multiple myeloma, Nikhil C. Munshi, MD, of Harvard Medical School, Boston, and his colleagues reported online Sept. 15 in JAMA Oncology.
Dana-Farber Cancer Institute
Dr. Nikhil C. Munshi
“This large cohort meta-analysis confirms that MRD status has prognostic value and is a valid surrogate marker for both PFS [progression-free survival] and OS [overall survival] in patients with multiple myeloma, including those who had achieved a CR [complete response],” the researchers wrote, noting that all of the studies confirmed the impact of MRD status on outcome, indicating that the predictive value of MRD status was independent of the type of treatment used.
Of 1,273 patients from 14 studies that looked at the impact of MRD status on PFS, 660 were MRD-negative and 613 were MRD-positive. Of 1,100 patients from 12 studies that looked at the impact of MRD on OS, 599 were MRD-negative, and 501 were MRD-positive. MRD-negative vs. -positive status was associated with better PFS and OS (hazard ratio, 0.41 and 0.57, respectively).
“Median PFS was 54 months for MRD-negative patients and 26 months for MRD-positive patients; median OS was 98 and 82 months, respectively,” the researchers wrote (JAMA Oncol. 2016 Sep 15. doi: 10.1001/jamaoncol.2016.3160).
Further, to evaluate the impact of MRD status on PFS and OS in patients who achieved conventional CR, they analyzed data from five studies looking at PFS in 396 MRD-negative and 178 MRD-positive patients, and 6 studies looking at OS in 430 MRD-negative and 186 MRD-positive patients. In patients achieving CR, the presence of MRD predicted shorter PFS (HR, 0.44) and shorter OS (HR, 0.47), they said.
“Median PFS was 56 months for MRD-negative patients and 34 months for MRD-positive patients, and median OS was 112 and 82 months, respectively. The OS rate was higher for MRD-negative patients, compared with MRD-positive patients at 3 years (94% vs. 80%), 5 years (80% vs. 61%), and 7 years (67% vs. 47%),” they wrote.
Although none of the studies included in the analysis compared the effect of two different treatment approaches on MRD status, five did evaluate MRD status before and after autologous stem cell transplantation, and all indicated that the treatment increased the proportion of MRD-negative patients.
Maintenance therapy also appeared, based on some of the studies, to have a beneficial effect on MRD status. In one study, MRD-negative status was maintained in 96% of patients receiving thalidomide maintenance therapy vs. 69% of MRD-negative patients receiving no maintenance therapy.
Minimal residual disease status is already considered an important prognostic factor in patients with multiple myeloma, and testing could be used to monitor response to therapy and guide subsequent treatment decisions, the investigators wrote, noting that “recent development of multiparameter flow cytometry– and next-generation sequencing–based methods has allowed for MRD assessment in larger studies.”
The findings provide quantitative evidence to support the conceptual basis for integrating MRD assessment after initial treatment in clinical trials as a surrogate end point for PFS and/or OS and in clinical practice to aid in prognostication and to guide treatment. However, “integration of MRD testing into standard practice requires optimization and standardization of MRD assessment and standardization of its timing,” they said.
This study was supported by the National Institutes of Health, the Medical Research Council, and Celgene. Dr. Munshi reported consultancy positions and advisory committee memberships with Celgene, Takeda, Janssen, and Merck.