Long-Term Outcomes of Blinatumomab Treatment in Patients with MRD-Positive ALL

Conference Correspondent - ASH 2015 - Leukemia

Persistence of minimal residual disease (MRD) after first-line induction therapy is associated with a higher risk of relapse compared with achievement of complete MRD response in patients with acute lymphoblastic leukemia (ALL), underscoring the need for interventional strategies that can achieve complete MRD response. Blinatumomab, a bispecific T-cell engaging (BiTE®) CD19-directed antibody construct, treatment in patients with MRD+ ALL resulted in complete MRD response in 78% of patients, including elderly patients, those in second-line treatment, and those with high MRD burden.1 Results of the long-term 18-month follow-up analysis of this multicenter, open-label, phase 2 study were reported by Gökbuget and colleagues.2

Eligible patients included adults with ALL who had achieved hematologic complete response (CR, <5% blasts in bone marrow) and MRD ?10-3 following ?3 induction therapies; patients with central nervous system pathology or extramedullary disease, previous allogeneic hematopoietic stem-cell transplantation (HSCT), or Philadelphia chromosome–positive ALL eligible for tyrosine kinase inhibitors were excluded. A total of 116 patients received blinatumomab (15 µg/m2/day, continuous intravenous infusion for 4 weeks, 2-week break); MRD responders in cycle 1 received up to 3 additional cycles of blinatumomab or underwent HSCT. Following blinatumomab therapy, 88 (78%) patients achieved a complete MRD response and 90 (78%) patients underwent HSCT. At a median follow-up of 30.0 months, median overall survival (OS) was 36.5 months in the overall patient cohort; median OS was significantly higher in patients who achieved complete MRD response versus those who did not (38.9 vs 12.5; P = .005). Median relapse-free survival (RFS) was 18.9 months overall, and significantly longer in patients treated in first remission versus later (24.6 vs 11.0; P = .004). Patients who achieved a complete MRD response at cycle 1 had a significantly longer RFS versus those with incomplete MRD response (23.6 vs 5.7; P = .003). Median duration of response (DOR) was not reached (NR) overall; median DOR was significantly longer in patients who achieved MRD CR in cycle 1 (NR vs 17.2 months; P = .049) versus those who did not. Overall, 67% of patients were able to receive stem-cell transplant in continuous remission after blinatumomab treatment. Serious adverse events (AEs) that were treatment-related occurred in 52% of patients; grade 3 treatment-related AEs occurred in 29% of patients, and grade 4 in 22%. The most clinically relevant AEs were neurologic, including tremor (30%), aphasia (13%), dizziness (8%), ataxia (6%), paresthesia (6%), and encephalopathy (5%). Grade ?3 neurologic events led to treatment interruptions in 12 (10%) patients; median time to resolution of any neurologic event was 4 days. Treatment discontinuations due to treatment-related AEs were reported in 12% of patients. Based on these results, the authors concluded that single-agent blinatumomab treatment was effective in producing high MRD CRs and prolonging survival in patients with MRD+ ALL.

  1. Goekbuget N, et al. Blood. 2014;124:379.
  2. Gökbuget N, et al. ASH 2015. Abstract 680.