Impact of measurable residual disease on outcomes using a modified DFCI protocol for adults with BCR-ABL negative...

Adults with acute lymphoblastic leukemia (ALL) have been reported to have favorable outcomes with the pediatric-based DFCI protocol, but measurable residual disease (MRD) data were lacking. We retrospectively evaluated outcomes in all adults with ALL treated with the DFCI protocol, including a modified protocol for patients >age 60, over a 10-year period (n = 89) in a real-world setting. MRD was assessed post-induction using multiparameter flow cytometry (MPFS) with 0.01% sensitivity. The morphologic complete remission (CR) rate was 92% treated with DFCI vs. 65% with DFCI > 60 (p = 0.0015), due to a higher induction mortality due to sepsis in patients >age 60. The 5-year overall survival (OS) was 72% and disease-free survival (DFS) of the CR patients was 66%. The OS was inferior in patients who received DFCI > 60 vs. DFCI but the DFS was not different. The OS declined with increasing age group (18-35 vs. 36-60 vs. >60, p = 0.011). Patients who were MRD negative (<0.01%) post-induction had a 5-year DFS of 80% vs. 47% for those with MRD > 0.1% (p = 0.01); the 5-year OS was 90% for MRD negative patients vs. 62% for MRD > 0.1% (p = 0.039). The 5-year DFS outcomes by MRD were comparable in the B-ALL patients (77% vs. 48%, p = 0.047). In patients aged > 35 years, MRD > 0.1% also predicted for inferior DFS (78% vs. 34%, p = 0.036) but not in patients aged 18-35. For MRD+ patients there was no difference in DFS comparing patients transplanted in CR1 vs. non-transplanted patients. On multivariate analysis MRD post-induction remained a significant predictor of DFS (p = 0.007), while age group was not significant. In conclusion, MRD is a significant predictor of outcomes with DFCI. DFS and OS are high in MRD negative patients, without the use of blinatumomab.