The Relevance of Minimal Residual Disease Monitoring in Elderly Multiple Myeloma Patients
There is growing evidence to suggest that minimal residual disease (MRD) monitoring can help to tailor treatment for patients with multiple myeloma (MM). MRD monitoring may have particular utility in elderly patients, where is it more critical to consider achieving an optimal balance between efficacy and toxicity.
Researchers used an 8-color second-generation flow assay to monitor MRD among elderly MM patients (n = 163) included in the PETHEMA/GEM2010MAS65 trial. The study included sequential chemotherapy with 9 cycles of bortezomib/melphalan/prednisone (VMP) followed by 9 cycles of lenalidomide/low-dose dexamethasone (Rd), or alternating cycles of VMP and Rd up to 18 cycles. A single 8-color antibody combination was used to detect abnormal clonal plasma cells. In this study, MRD negativity was defined when <20 clonal plasma cells were detected among ?2,000,000 leukocytes. Median follow-up was 3 years, and time to progression (TTP) and overall survival (OS) were measured from the time of MRD assessment.
MRD-negative rates at cycle 9 of chemotherapy (n = 128) were similar between the sequential and alternating regimens (20% vs 24%; P = .37). Regardless of chemotherapy regimen, patients attaining MRD negativity at cycle 9 showed a significantly prolonged TTP (P = .001) and OS (P = .02) compared with patients with persistent MRD. After 18 cycles of treatment, MRD-negative rates were slightly (but not significantly) higher among patients randomized to the sequential versus alternating schema: 46% vs 33% (P = .19). When assessing the impact of MRD negativity among cytogenetically defined standard- and high-risk t(4;14), t(14;16), and del(17p) patient subgroups, standard-risk patients attaining MRD negativity had significantly prolonged TTP compared with MRD-positive patients (P <.001). Interestingly, high-risk cytogenetic patients reaching MRD negativity also showed significantly superior TTP. Finally, researchers assessed whether patient age impacted TTP in the context of attaining MRD negativity. While median TTP was not reached for patients aged 65 to 75 and 75 to 80 years reaching MRD negativity, it became progressively shorter (32, 28, and 22 months) for MRD-positive patients aged 65 to 75 versus 75 to 80 versus >80 years, respectively (P <.001). Only 2 patients aged >80 years reached MRD negativity.
Researchers concluded that the clinical impact of depth of response including MRD negativity in elderly MM patients translated into significantly improved survival regardless of patients’ age and cytogenetic risk. Conversely, MRD positivity was associated with poorer outcomes in patients with standard-risk MM as well as those achieving complete response. These findings add to the evidence indicating that treatment individualization by MRD status may contribute to improved survival in patients with MM.