On March 29, 2018 the FDA granted Amgen Inc. approval to market BLINCYTO® (blinatumomab) for the treatment of adult and pediatric patients with minimal residual disease (MRD)-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission (CR) . MRD detection in patients with ALL who have achieved a CR is an indicator of chemotherapy resistance and a risk factor for hematologic relapse, thus achieving MRD-negativity after chemotherapy is an important treatment goal . Blinatumomab is a bispecific antibody, known as a CD3 T-cell engager, that binds to T-cells and directs them to CD19-positive cells (most B-cell precursors), which can then stimulate and/or enhance T-cell immune responses against CD19-expressing cells . Blinatumomab was originally approved in 2014 for the treatment of relapsed or refractory Philadelphia chromosome-negative ALL .
The approval to treat MRD-positive ALL was based on a single-arm, multicenter phase 2 study investigating the safety and efficacy of blinatumomab in patients with MRD-positive B-cell precursor ALL who had received at least three cycles of standard chemotherapy (NCT01207388) . A total of 116 patients received blinatumomab daily for up to four cycles. Of those who were evaluable (n=113), 78% achieved a complete MRD-negative response which was associated with a longer relapse-free survival (23.6 vs 5.7 months) and overall survival (38.9 vs 12.5 months) compared to those who did not achieve MRD-negativity on study . Blinatumomab was well tolerated with the most common grade 3 or 4 adverse events being neurological events (13%) and cytokine release syndrome grade (2%) . This is a groundbreaking study assessing MRD-negativity as a primary endpoint, provides support for the need to achieve MRD-negativity and the use of blinatumomab to help achieve that goal.
- BLINCYTO® (blinatumomab) for injection, for intravenous use. Drugs@FDA: FDA Approved Drug Products 03/29/2018 [cited 2018 May 4]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125557s013lbl.pdf.
- Berry, D.A., et al., Association of Minimal Residual Disease With Clinical Outcome in Pediatric and Adult Acute Lymphoblastic Leukemia: A Meta-analysis. JAMA Oncol, 2017. 3(7): p. e170580.
- Gokbuget, N., et al., Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood, 2018. 131(14): p. 1522-1531.
- BLINCYTO (blinatumomab) for injection, for intravenous use. Initial U.S. Approval: 2014 Drugs@FDA: FDA Approved Drug Products 12/03/2014 [cited 2018 May 3]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125557lbl.pdf.
- Confirmatory Phase II Study of Blinatumomab (MT103) in Patients With Minimal Residual Disease of B-precursor Acute Lymphoblastic Leukemia (ALL) (BLAST). ClinicalTrials.gov May 1, 2017 [cited 2018 May 3]; Available from: https://clinicaltrials.gov/ct2/show/NCT01207388.