In multiple myeloma (MM), there is a growing body of evidence showing the importance of minimal residual disease (MRD) monitoring, particularly among transplant-ineligible patients. Paiva and colleagues assessed the clinical relevance of MRD monitoring in 163 elderly MM patients enrolled in the PETHEMA/GEM2010MAS65 trial of sequential bortezomib/melphalan/prednisone (VMP) followed by a lenalidomide/low-dose dexamethasone (Rd) regimen for 9 cycles each, or alternating cycles of VMP and Rd up to 18 cycles.1 MRD negativity was defined as <20 clonal plasma cells detected among ≥2,000,000 leukocytes (<0.001%; limit of detection: 10-5) using an 8-color second-generation flow assay.
At a median follow-up of 3 years, there was no difference in MRD-negative rates between the sequential and alternating regimens (20% vs 24%; P = .37) at cycle 9. Patients attaining MRD negativity at cycle 9 demonstrated a significant prolongation in time to progression (TTP; median: not reached [NR] vs 35 months; P = .001), which translated to overall survival (OS) improvement (100% vs 68% at 2 years; P = .01) compared with those with persistent MRD. MRD persistence at cycle 9 in patients who achieved complete response (CR; n = 43) was associated with significantly inferior OS (100% vs 74% at 3 years; P = .02). Among patients with paired MRD assessments at cycles 9 and 18, 19% of MRD-positive patients at cycle 9 became MRD-negative at cycle 18, whereas all MRD-negative patients at cycle 9 remained negative at cycle 18. At the end of cycle 18 (n = 119), MRD-negative rates were numerically higher in the sequential treatment cohort (46% vs 33%; P = .19). Patients who achieved CR plus MRD negativity at cycle 9 showed significantly longer TTP compared with those with CR and MRD-positive disease (NR vs 42 months). When the impact of MRD negativity was assessed among patients with standard- and high-risk cytogenetics, those who achieved MRD negativity showed significantly prolonged TTP versus MRD-positive patients regardless of whether they had standard-risk (median, 40 months vs 31 months; P = .002) or high-risk (median, NR vs 26 months; P = .007) cytogenetics. However, the benefit was greater for the high-risk cytogenetics group. When assessed by patient age, patients who achieved MRD negativity showed improved survival outcomes regardless of age, but those with MRD positivity showed significantly decreased survival with increasing age (65-75 years: 32 months; 75-80 years: 28 months; >80 years: 22 months; P <.001). Based on these results, it was concluded that MRD negativity in elderly MM patients translated to significant improvements in survival irrespective of patients’ age and cytogenetic risk. Conversely, patients with standard-risk MM and those in complete remission but remaining MRD-positive experience poorer clinical outcomes and warrant individualization of their treatment to improve their survival.
- Paiva B, et al. ASH 2015. Abstract 4181.