Minimal residual disease in patients with diffuse large B-cell lymphoma undergoing autologous stem cell transplantation.

Improved biomarkers are needed to guide the optimal use of autologous stem cell transplantation (ASCT) for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We hypothesized that minimal residual disease (MRD) identified using immunoglobulin high-throughput sequencing in apheresis stem cell (ASC) samples or post-ASCT peripheral blood mononuclear cell (PBMC) and plasma samples could predict relapse. We studied 159 patients with R/R DLBCL who underwent ASCT, of whom 98 had an ASC sample and 60 had post-ASCT surveillance samples. After a median post-ASCT follow-up of 60 months, the 5-year progression-free survival (PFS) was 48%. MRD was detected in 23/98 (23%) ASC samples and was associated with very poor PFS (5-year PFS 13% vs 53%, p<0.001) and inferior overall survival (52% vs 68%, p=0.05). The sensitivity and specificity of ASC MRD positivity for progression or death were 36% and 93%, respectively. Positive ASC MRD remained a significant predictor of PFS in a multivariable analysis (hazard ratio [HR] 3.7, p<0.001). Post-ASCT surveillance MRD testing from plasma, but not PBMC samples, reliably identified patients with impending relapse. A positive plasma MRD result was associated with inferior PFS (HR 3.0, p=0.016) on a multivariable analysis. The median lead time from MRD detection to relapse was 62 days (range 0-518 days). In conclusion, detection of MRD in ASC samples is associated with a very high relapse risk, justifying alternative treatment strategies or trials of novel consolidation options in those patients. Furthermore, post-ASCT MRD monitoring may facilitate trials evaluating early initiation of treatment at molecular relapse. This trial is registered at www.clinicaltrials.gov as NCT02362997.