Blinatumomab Granted Full Approval to Treat Relapsed or Refractory B-cell Precursor ALL in Adults and Children


On July 11, the U.S. Food and Drug Administration (FDA) approved the supplemental Biologics License Application (sBLA) for blinatumomab (Blincyto) to include overall survival data from the phase III TOWER study. The approval converts blinatumomab's accelerated approval to a full approval. The sBLA approval also included data from the phase II ALCANTARA study, which supported the treatment of patients with Philadelphia chromosome (Ph)-positive relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). The approval expands the indication of blinatumomab for the treatment of relapsed or refractory B-cell precursor ALL in adults and children.

Blinatumomab is the first and only FDA-approved CD19-directed CD3 bispecific T-cell engager (BiTE) immunotherapy, as well as the first bispecific antibody construct from Amgen's BiTE platform. In 2014, the drug was granted Breakthrough Therapy designation and accelerated approval to treat patients with Ph-negative relapsed or refractory B-cell precursor ALL, and in 2016, it received accelerated approval to treat pediatric patients with Ph-negative relapsed or refractory B-cell precursor ALL. The current approval is the first to include Ph-positive disease.

“For researchers and physicians, overall survival is the primary goal of treatment and the gold standard of outcomes, demonstrating a clear value to patients,” said Anthony Stein, MD, study investigator and Co-Director of the Gehr Family Center for Leukemia Research at City of Hope.
“Data from the TOWER study support the use of this single-agent bispecific T-cell engager immunotherapy, the first to demonstrate superior overall survival in patients with Ph-negative relapsed or refractory B-cell precursor ALL, offering a much-needed alternative with significantly improved outcomes over standard of care chemotherapy.”

“Relapsed or refractory ALL is often a lethal disease, with a median overall survival of just 4 months on standard-of-care chemotherapy,” said Bijal D. Shah, MD, a medical oncologist at the Moffitt Cancer Center. “As a physician, my goal is to identify treatments that improve response rates in patients with aggressive hematologic malignancies. Blinatumomab is an option that has been shown to help these high-risk patients fight their disease.”


The approval is based on results from the TOWER study, a phase III, randomized, active-controlled, open-label study investigating the efficacy of blinatumomab vs standard-of-care chemotherapy in 405 adult patients with Ph-negative relapsed or refractory B-cell precursor ALL.

The study enrolled a difficult-to-treat patient population, which included patients from several stages of relapse. In the blinatumomab arm, this included 35% of patients that had relapsed post–allogenic hematopoietic stem cell transplant (alloHSCT), and excluded those with late first relapse (≥ 12 months after initial remission). Patients were randomized in a 2:1 ratio to receive blinatumomab (n = 271) or treatment with investigator's choice of standard-of-care chemotherapy (n = 134). The determination of efficacy was based on overall survival. Per the recommendation of an independent data monitoring committee, Amgen ended the study early for evidence of superior efficacy in the blinatumomab arm vs standard-of-care chemotherapy.

The trial found that blinatumomab demonstrated a superior improvement in median overall survival over standard of care chemotherapy, nearly doubling median overall survival. The study showed that median overall survival was 7.7 months (95% confidence interval [CI] = 5.6–9.6) for blinatumomab vs 4 months (95% CI = 2.9–5.3) for standard of care (hazard ratio for death = 0.71; P = .012).


The current approval is also based on data from the ALCANTARA study, a phase II, single-arm, multicenter, open-label study investigating the efficacy of blinatumomab in 45 adult patients with Ph-positive B-cell precursor ALL, who had relapsed after or were refractory to at least 1 second-generation or later tyrosine kinase inhibitor, or were intolerant to second-generation or later tyrosine kinase inhibitors and intolerant or refractory to imatinib. Blinatumomab was administered in 28-day cycles by continuous intravenous infusion. Efficacy was based on the complete remission rate, duration of complete remission, and proportion of patients with an minimal residual disease–negative complete remission or complete remission with partial hematologic recovery within two cycles.

Safety and Adverse Events

The FDA-approved prescribing information for blinatumomab includes a boxed warning for cytokine-release syndrome and neurologic toxicities. Blinatumomab is also under a risk evaluation and mitigation strategy (REMS) program in the United States.

Safety results among patients who received blinatumomab were comparable to those seen in the phase II studies in adult patients with Ph-negative relapsed or refractory B-cell precursor ALL. For the most common adverse events (≥ 10% incidence rate) in the blinatumomab arm, six events (pyrexia, infusion-related reaction, cough, cytokine-release syndrome, tremor, decreased immunoglobulins) occurred at an incidence rate that was at least 5% higher for blinatumomab compared to standard-of-care chemotherapy.

“We are pleased that the FDA has granted full approval for blinatumomab, marking a significant milestone for certain patients with relapsed or refractory ALL,” said Sean E. Harper, MD, Executive Vice President of Research and Development at Amgen. “This approval supports the use of blinatumomab in a broader spectrum of patients, including those with few options to date, such as those with Philadelphia chromosome–positive disease, and reinforces the potential of the BiTE platform as a novel approach to immuno-oncology.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.