FDA Gives Full Approval to Blinatumomab in MRD-Positive B-Cell ALL


Blinatumomab has been granted full approval by the FDA for patients with B-cell acute lymphoblastic leukemia and minimal residual disease of 0.01% or more.

The approval for blinatumomab is based on results of the phase 3 BLAST (NCT01207388) trial and the phase 3 ECOG-ACRIN E1910 trial (NCT02003222).

The FDA has granted full approval to blinatumomab (Blincyto) for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia

The FDA has granted full approval to blinatumomab (Blincyto) for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (B-ALL) that is in first or second complete remission with minimal residual disease (MRD) of 0.1% or more, according to a press release from Amgen.1

The full approval is based on results from the phase 3 ALL1331 trial (NCT02101853) and the phase 3 20120215 trial (NCT02393859).2,3 In March 2018, the FDA granted accelerated approval to the agent based on results from the phase 2 BLAST (NCT01207388) trial.4 Additionally, results from the phase 3 ECOG-ACRIN E1910 trials (NCT02003222) was presented at the 2022 American Society Hematology Annual Meeting.5

"We are pleased the FDA has granted full approval for [blinatumomab], the first FDA-approved CD19-directed CD3 T-cell engager BiTE [bispecific T-cell engager] immunotherapy and the first to be FDA-approved for MRD in 2018," David M. Reese, MD, executive vice president of Research and Development at Amgen, said in the press release. "Today’s full approval underscores the clinical benefit of [blinatumomab] for people living with B-ALL, and we look forward to exploring how we can continue to make a significant impact for these patients."

AALL1331 Trial in Pediatric Population

In this trial, 255 patients with low-risk ALL were enrolled and randomly assigned to either the 2/block 2/2 continuation cycles of chemotherapy then maintence or 2 cycles of continuation chemotherapy with 3 blocks of blinatumomab and maintenance.

Additionally, if patients had central nervous sytem luekmia, they received 18 Gy of cranial radiation during maintenance which intensified during intrathecal chemotherapy.

The 4-year disease-free survival was 61.2% ± 5.0% in the blinatumomab arm vs 49.5% ± 5.2% in the chemotherapy arm (P = 089), with the overall survival (OS) being 90.4% ± 3.0% vs 79.6% ± 4.3% (P = .11).

Event-Free Survival Analysis

In the 20120215 trial, patients aged between 28 days and 18 years with morphologic complete remission of less than 5% or more than 5%. Patients were given 1 cycle of blinatumumab at 15 μg/m2 per day for 4 weeks with an intravenous infusion or chemotherapy for the third consolidation.

Of the 108 patients randomized, the median follow-up was 22.4 months and the incidence of events in the blinatumumab arm was 31% vs 57% in the chemotherapy arm (HR, 0.33; 95% CI, 0.18-0.61; log-rank P <.001).

The OS HR was 0.43, an MRD remission was observed in 90% of patients in the blinatumumab group vs 54% in the chemotherapy group.

Blinatumomab Received Accelerated Approval Due to BLAST Trial Results

This was a single-arm confirmatory, multicenter trial examining the safety and efficacy of blinatumomab in the aforementioned patient population. The primary end point was the percentage of patients with minimal residual disease and secondary end points included hematological relapse-free survival, overall survival, and 100-day mortality after allogeneic hematopoietic stem cell transplant.

Patients were eligible for treatment if they had complete hematologic remission after at least 3 intense chemotherapy blocks, the presence of MRD disease at 10-3 or greater, and have available bone marrow for primary diagnosis. Patients were excluded from the study if they had the presence of circulating blasts or current extra-medullary involvement by ALL, a history of central nervous system pathology, or prior allogeneic HSCT.

Blinatumomab was given to patients at a dose of 15 μg/m2 per day intravenously during all treatment cycles up to 4 cycles.

Among those having their first complete response (CR1), 74% of patients underwent an allogeneic HSCT along with 56% of those in their second CR (CR2) with continuous hematologic complete remission.

Additionally, 85% (95% CI, 74%-93%) of patients in CR1 were MRD-negative compared, as were 72% (95% CI, 51%-88%) in CR2. Patients had a median estimated median hematological relapse-free survival of 35.2 months in CR1, and in CR2 the median was 12.3 months.

Adverse effects (AEs) occurred in about 20% of patients, and included pyrexia, infusion-related reactions, headaches, infections, tremors, and chills. Serious AEs occurred in 61% of patients, with the most common occurring in 2% of patients being pyrexia, tremor, encephalopathy, aphasia, lymphopenia, neutropenia, overdose, device related infection, seizure, and staphylococcal infection.

Grade 3 or higher AEs occurred in 64% of patients. In total, 17% of patients discontinued therapy because of neurologic events. Two fatal AEs occurred within 30 days of the end of treatment.

Findings From the Phase 3 ECOG-ACRIN E1910

At the 2022 ASH Annual Meeting, results from the trial were presented that showed the median OS was not reached in the blinatumomab plus chemotherapy group vs 71.4 months in the chemotherapy along group (hazard ratio [HR], 0.42; 95% CI, 0.24-0.75; P = .003).

At a median of 3.5 years, the OS rates were 83% in the combination group compared with 65% in the chemotherapy alone group.

In this trial, standard induction chemotherapy was administered for 2 months until a remission was achieved. This was then followed by chemotherapy intensification for 1 month in to treat leukemia in the central nervous system. Additionally, 224 patients were randomized to receive blinatumomab for 2 monthly cycles intravenously then 4 months of consolidation chemotherapy and either 2 months of blinatumomab (n = 112) or 4 months of standard consolidation chemotherapy (n = 112). Patients also received 2.5 years of maintenance chemotherapy.

If patients had been newly diagnosed and were between 30 to 70 years old, were BCR-ABL1–negative, and had B-lineage ALL, they were tested for MRD by 6-color flow cytometry during randomization.

Overall, 22 patients went on to received allogenic HSCT.

In total, 17 patients in the blinatumomab arm died from either relapse (n = 8), or non-relapse mortality (n = 9) compared with 39 deaths in the chemotherapy arm due to either relapse (n = 20), non-relapse mortality (n = 17), or other unknow causes (n = 2).


  1. FDA grants full approval for Blincyto (blinatumomab) to treat minimal residual disease-positive B-cell precursor acute lymphoblastic leukemia. News release. Amgen. June 21, 2023. Accessed June 21, 2023. https://bit.ly/3XjCsbG
  2. Hogan LE, Brown PA, Ji L, et al. Children's Oncology Group AALL1331: Phase III trial of blinatumomab in children, adolescents, and young adults with low-risk B-cell ALL in first relapse. J Clin Oncol. May 31, 2023;JCO2202200. doi:10.1200/JCO.22.02200
  3. Locatelli F, Zugmaier G, Rizzari C, et al. Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325(9):843-854. doi:10.1001/jama.2021.0987
  4. FDA granted accelerated approval to blinatumomab (Blincyto, Amgen Inc.) for the treatment of adult and pediatric patients with B-cell precursor acute lymphoblastic leukemia. News release. FDA. March 29, 2018. Accessed June 21, 2023. https://bit.ly/3Xi3gJk
  5. Litzow MR, Sun Z, Paletta E, et al. Consolidation therapy with blinatumomab improves overall survival in newly diagnosed adult patients with B-Lineage acute lymphoblastic leukemia in measurable residual disease negative remission: results from the ECOG-ACRIN E1910 randomized Phase III National Cooperative Clinical Trials Network Trial. Blood. 2022;140(suppl 2):LBA-1. doi:10.1182/blood-2022-171751
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