ECOG-ACRIN E1910: adding blinatumomab to chemotherapy for adults with B-cell ALL already in MRD-negative remission
Giving the bispecific blinatumomab to adults whose leukaemia was already undetectable after chemotherapy raised three-year survival from 68% to 85%.
E1910 enrolled adults aged 30-70 with newly diagnosed Philadelphia-chromosome-negative B-cell ALL. Those who reached MRD-negative remission after induction and intensification (224 patients) were randomised to four cycles of blinatumomab interleaved with consolidation chemotherapy or chemotherapy alone, followed by maintenance. The primary endpoint in this group was overall survival. At three years OS was 85% versus 68% (hazard ratio 0.41) and relapse-free survival 80% versus 64%. Neuropsychiatric events were more frequent with blinatumomab but mostly low grade. The result led to approval of blinatumomab in consolidation for CD19-positive B-ALL regardless of MRD status.
- 488 adults enrolled; 224 MRD-negative patients randomised to blinatumomab plus chemotherapy or chemotherapy alone.
- 3-year overall survival 85% vs 68%; hazard ratio 0.41.
- 3-year relapse-free survival 80% vs 64%.
- Benefit seen across age groups, including patients aged 55-70.
- Grade 3 or higher neuropsychiatric events higher with blinatumomab; no excess treatment-related deaths.
E1910 changed the standard of care for adult B-ALL: immunotherapy is now part of front-line consolidation even for patients with no detectable leukaemia, because MRD-negative by flow cytometry does not mean cured. It also demonstrated that a T-cell engager can improve overall survival in a curative setting. Chemotherapy-light or chemotherapy-free regimens built on blinatumomab and inotuzumab are the next step.
- MRD was assessed by flow cytometry at 10^-4 sensitivity; more sensitive NGS assays might identify who truly needs blinatumomab.
- Adults under 30 were excluded (treated on paediatric-inspired protocols).
- Randomised sample was modest and the OS benefit emerged at interim analysis.
- Blinatumomab requires continuous 28-day infusions, a logistical burden.