BLAST

Background

Phase 2, multicenter, single-arm confirmatory trial (BLAST). N=116 adults (≥18 years) with B-cell precursor (BCP) ALL in hematologic complete remission (CR) with quantifiable MRD (≥10⁻³ or ≥0.1%) by PCR after ≥3 induction/consolidation chemotherapy cycles. Blinatumomab was administered in an MRD-positive CR setting (not relapsed/refractory) to evaluate MRD eradication and its impact on survival. FDA approved blinatumomab for MRD-positive ALL based on this trial. Published Blood 2018.

Interventions and follow up

Regimen: Blinatumomab 15 µg/m²/d CIV × 28d every 6 weeks for up to 4 cycles in adults with B-ALL in hematologic CR with persistent or recurrent MRD (≥10⁻³)
Primary endpoint: Complete MRD response (MRD negativity by PCR) after cycle 1
mFollow up: Not reported in Blood 2018 primary report

Results

Complete MRD response after cycle 1 (primary endpoint): 78% (88/113 evaluable; 95% CI 69–85%)
Overall MRD CR rate (any cycle): ~80%
mOS (all patients): 36.5 months
mRFS (MRD responders vs non-responders): 23.6 vs 5.7 months, P=.002
mOS (MRD responders vs non-responders): 38.9 vs 12.5 months, P=.002
Allo-HSCT (in CR following MRD response): ~54% of patients

Adverse events

Neurologic: Grade 3–4 neurologic events 13% (primarily encephalopathy, headache); managed with dexamethasone and dose interruptions
CRS: Grade ≥3 CRS 3% (4 patients)
Hematologic/other: Cytopenia during infusion period; no treatment-related deaths attributed to blinatumomab

Conclusions

Blinatumomab eradicated MRD in 78% of adults with MRD-positive BCP-ALL in CR. MRD response was strongly associated with prolonged RFS (23.6 vs 5.7 months) and OS (38.9 vs 12.5 months), validating MRD negativity as a clinically meaningful surrogate endpoint in adult ALL and supporting blinatumomab as standard therapy for MRD-positive disease in remission.

Key Limitations

Single-arm design with no randomized comparator; survival benefit inferred from MRD-responder vs non-responder comparison, which is subject to guarantee-time and selection bias. Approximately half of patients proceeded to allo-HSCT, confounding the attribution of long-term survival to blinatumomab alone. Heterogeneous prior therapy. MRD quantified by PCR only.

Clinical Context

BLAST supported the FDA approval (March 2018) of blinatumomab for adults and children with BCP-ALL in first or second CR with MRD ≥0.1% — the first agent approved for an MRD-positive indication in any malignancy. EMA followed. ELN and ESMO guidance endorse MRD-directed blinatumomab for persistent/recurrent MRD in CR, typically as a bridge to allo-HSCT.

References