MRD Negativity Post-AHCT Linked to Improved Multiple Myeloma Survival

Minimal residual disease (MRD) negativity after autologous hematopoietic cell transplantation (AHCT) was associated with significantly longer progression-free survival (PFS) and overall survival (OS) among patients with multiple myeloma, regardless of molecular risk status and the use of lenalidomide maintenance therapy, according to a recent study.

The study evaluated data from a large phase III trial of patients randomly assigned to receive lenalidomide maintenance or no maintenance at 3 months post-AHCT. MRD status was assessed before random assignment (AHCT+3) and 6 months later (AHCT+9).

At AHCT+3, 63.3% of patients were MRD-negative. MRD negativity was associated with improved PFS (hazard ratio [HR]=0.47; 95% CI, 0.37-0.58; P<.001) and OS (HR=0.59; 95% CI, 0.40-0.85; P=.046). These benefits were sustained at AHCT+9 (PFS HR=0.20; 95% CI, 0.13-0.31; P<.001 and OS HR=0.33; 95% CI, 0.15-0.75; P=.0077).

Patients with sustained MRD negativity at AHCT+3 or AHCT+9, or those whose disease converted to MRD negativity by AHCT+9, had the longest PFS and OS.

Patients assigned to lenalidomide maintenance were more likely to convert from being MRD-positive before maintenance to MRD-negative 6 months later. High-risk features had an adverse effect on both PFS and OS, even among those with MRD-negative status. MRD-negative patients with one or more high-risk lesions had a shorter median PFS compared with MRD-negative standard-risk patients (P=.0002). On multivariable analysis of MRD status, maintenance therapy and molecular risk maintained prognostic impact at both AHCT+3 and AHCT+9.

Based on these results, the researchers wrote that “achievement of MRD negativity at [AHCT]+9 may be considered a key treatment goal.”

de Tute RM, Pawlyn C, Carins DA, et al. 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. doi:10.1200/JCO.21.02228