Although many patients with multiple myeloma (MM) achieve a complete response (CR) with treatment, the likelihood of relapse is still high, suggesting the presence of minimal residual disease (MRD) that cannot be detected via conventional assessments. The heterogeneity among MRD detection techniques, though, hinders their clinical interpretation. To assess the role MRD status plays in survival outcomes for patients with MM, Nikhil C. Munshi, MD, and colleagues conducted a meta-analysis of 18 studies involving patients with newly diagnosed MM.
Dr. Munshi, director of Basic and Correlative Science at the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston, Massachusetts, presented these data at the 15th International Myeloma Workshop.
To identify the published articles for the meta-analysis, Dr. Munshi and colleagues searched PubMed for studies published between January 1990 and September 2014 that included 20 or more patients with newly diagnosed MM who required treatment and who had MRD evaluation results. If primary data were not available, survival graphs were used to evaluate individual survival. A total of 302 articles were reviewed, 18 of which reported on overall survival (OS) or progression-free survival (PFS) in addition to MRD status.
A total of 2,208 patients were identified, and MRD was evaluated via:
- Multiparameter flow cytometry (n=1,606)
- Polymerase chain reaction (n=492)
- High-throughput sequencing (n=110)
Nine studies reported on conventional CR at the time of MRD measurement, while four articles represented unique datasets. A total of 496 evaluable patients were ultimately included: 362 who were MRD-negative and 134 who were MRD-positive.
Overall, the presence of MRD was associated with shorter PFS (hazard ratio [HR] = 0.44; 95% CI 0.33-0.58; p<0.0001), and the median PFS was longer for MRD-negative than MRD-positive patients (60 months vs. 36 months).
MRD-negative patients were also more likely than MRD-positive patients to achieve longer PFS:
- Three-year PFS: 72% and 50%, respectively
- Five-year PFS: 50% and 29%, respectively
Absence of MRD significantly reduced the risk of death by 54 percent compared with MRD-positive patients (HR=0.46; 95% CI 0.31-0.68; p=0.0002) and, although the median OS was not reached for MRD-negative patients, the median OS for MRD-positive patients was 82 months.
At three years, the rate of OS was higher for MRD-negative patients compared with MRD-positive patients: 93 percent versus 79 percent, respectively. Similarly, at five years, the rates of OS were 78 percent and 60 percent, respectively.
“These results show that MRD negativity predicted for substantially better PFS and OS in patients with MM who had achieved CR,” the researchers concluded, suggesting that MRD status is an important marker of long-term outcomes in patients with MM. “MRD status is a key exploratory endpoint in MM clinical trials and its role as a surrogate marker of OS should be actively pursued.”
Munshi N, Avet-Loiseau H, Rawstron A, et al. A meta-analysis investigating the impact of minimal residual disease (MRD) status on survival outcomes in patients with multiple myeloma (MM) who achieve complete response (CR). Abstract OP-001. Presented at the 15th International Myeloma Workshop, September 23, 2015; Rome, Italy.