Molecular response with blinatumomab in relapsed/refractory B-cell precursor acute lymphoblastic leukemia

Minimal residual disease (MRD), where leukemic cell levels are lower than the morphologic detection threshold, is the most important prognostic factor for acute lymphoblastic leukemia (ALL) relapse during first-line chemotherapy treatment and is standard of care in treatment monitoring and decision making. Limited data are available on the prognostic value of MRD response after relapse. We evaluated the relationship between MRD response and outcomes in blinatumomab-treated adults with relapsed/refractory (R/R) B-cell precursor ALL. Of 90 patients with complete remission (CR) or CR with partial hematologic recovery (CRh), 64 (71.1%) achieved a complete MRD response (no detectable individual rearrangements of immunoglobulin/T-cell receptor genes by polymerase chain reaction [PCR] at a minimum sensitivity level of 10-4). Eleven patients had MRD <10-4. Therefore, overall, 75 (83.3%) experienced an MRD response (no detectable MRD or detectable MRD) measured by PCR within the first 2 treatment cycles. Overall survival (OS) and relapse-free survival (RFS) were significantly longer in patients who achieved CR/CRh and MRD response (median, 20.6 and 9.0 months, respectively) compared with CR/CRh patients without MRD response (median, 12.5 and 2.3 months, respectively). In conclusion, longer durations of OS and RFS associated with MRD response support the value of achieving MRD response and its use as a prognostic factor for blinatumomab treatment in R/R ALL. This trial was registered at www.clinicaltrials.gov as #NCT01466179.