KEY TAKEAWAYS
- The phase III Myeloma XI study analyzed the prognostic impact of MRD at serial time points in patients with multiple myeloma undergoing maintenance therapy.
- The MRD status of patients was assessed using flow cytometry at two-time points: ASCT + 3 and ASCT + 9, the sensitivity of the MRD assessment was 0.004%.
- MRD negativity at ASCT + 3 and ASCT + 9 was strongly associated with better PFS and OS in patients with multiple myeloma.
- Patients assigned to lenalidomide maintenance therapy were more likely to convert from MRD-positive to MRD-negative at ASCT + 9 than those in the observation group (30% vs. 17%).
- The MRD status at ASCT + 3 and ASCT + 9 is a powerful predictor of PFS and OS in patients with multiple myeloma.
Minimal residual disease (MRD) can predict outcomes in patients with multiple myeloma; however, there are limited data on the prognostic impact of MRD when assessed at serial time points in the context of maintenance therapy after autologous stem-cell transplant (ASCT) and the interaction of MRD and molecular risk. The relationship between MRD status, progression-free survival (PFS), and overall survival (OS) in post-ASCT patients randomly assigned to lenalidomide maintenance or no maintenance 3 months after ASCT was analyzed using data from a significant phase III trial (Myeloma XI). Before random maintenance assignment (ASCT + 3) and 6 months later (ASCT + 9), MRD status was determined by flow cytometry (median sensitivity 0.004%).
At ASCT + 3, 475 of 750 (63.3%) patients were MRD-negative, compared to 275 (36.7%) patients who were MRD-positive. MRD negativity was associated with better PFS (hazard ratio [HR] = 0.47; 95% confidence interval [CI]: 0.37 to 0.58; P< .001) and OS (HR = 0.59; 95% CI: 0.40 to 0.85; P =.0046). At ASCT + 9, 214 out of 326 (65.6%) were MRD-negative, while 112 were MRD-positive. MRD negativity was related to enhanced PFS (HR = 0.20; 95% CI, 0.13 to 0.31; P< .0001) and OS (HR = 0.33; 95% CI, 0.15 to 0.75; P =.0077). The findings were remarkably similar when limited to patients with a complete or nearly complete response. The most prolonged PFS/OS was associated with sustained MRD negativity from ASCT + 3 to ASCT + 9 or the conversion to MRD negativity by ASCT + 9. Patients randomly assigned to lenalidomide maintenance were more likely to convert from MRD-positive to MRD-negative six months after random assignment (lenalidomide 30%, observation 17%). High-risk molecular characteristics harmed PFS and OS even among patients with MRD-negative status. On multivariable analysis of MRD status, maintenance therapy and molecular risk maintained their prognostic impact at ASCT + 3 and ASCT + 9-time points. MRD status at ASCT + 3 and ASCT + 9 potently predicts PFS and OS in patients with multiple myeloma.
Source: https://pubmed.ncbi.nlm.nih.gov/35377708/
Clinical Trial: http://clinicaltrials.gov/show/NCT01554852
De Tute RM, Pawlyn C, Cairns DA, Davies FE, Menzies T, Rawstron A, Jones JR, Hockaday A, Henderson R, Cook G, Drayson MT, Jenner MW, Kaiser MF, Gregory WM, Morgan GJ, Jackson GH, Owen RG. Minimal Residual Disease After Autologous Stem-Cell Transplant for Patients With Myeloma: Prognostic Significance and the Impact of Lenalidomide Maintenance and Molecular Risk. J Clin Oncol. 2022 Sep 1;40(25):2889-2900. doi: 10.1200/JCO.21.02228. Epub 2022 Apr 4. PMID: 35377708.
