FDA Expands Approval of Blinatumomab for Certain Patients With B-Cell Precursor ALL
The U.S. Food and Drug Administration granted accelerated approval to blinatumomab (Blincyto) to treat adults and children with B-cell precursor acute lymphoblastic leukemia (ALL) who are in remission but still have minimal residual disease (MRD). In patients who have achieved remission after initial treatment for this type of ALL, the presence of MRD increases their risk of relapse.
“This is the first FDA-approved treatment for patients with MRD-positive ALL,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Because patients who have MRD are more likely to relapse, having a treatment option that eliminates even very low amounts of residual leukemia cells may help keep the cancer in remission longer. We look forward to furthering our understanding about the reduction in MRD after treatment with [blinatumomab]. Studies are being conducted to assess how [blinatumomab] affects long-term survival outcomes in patients with MRD.”
Blinatumomab works by attaching to CD19 protein on the leukemia cells and CD3 protein found on certain immune system cells. Bringing the immune cell close to the leukemia cell allows the immune cells to attack the leukemia cells better. The FDA first approved blinatumomab under accelerated approval in December 2014 for the treatment of Philadelphia chromosome–negative relapsed or refractory positive B-cell precursor ALL. Full approval for this indication was granted in July 2017, and at that time, the indication was also expanded to include patients with Philadelphia chromosome–positive ALL.
Safety and Efficacy
The efficacy of blinatumomab in MRD-positive ALL was shown in a single-arm clinical trial that included 86 patients in first or second complete remission who had detectable MRD in at least 1 out of 1,000 cells in their bone marrow. Efficacy was based on achievement of undetectable MRD in an assay that could detect at least 1 cancer cell in 10,000 cells after 1 cycle of blinatumomab treatment, in addition to the length of time that the patients remained alive and in remission (hematologic relapse-free survival). Overall, undetectable MRD was achieved by 70 patients. Over half of the patients remained alive and in remission for at least 22.3 months.
The side effects of blinatumomab when used to treat MRD-positive B-cell precursor ALL are consistent with those seen in other uses of the drug. Common side effects include infections (bacterial and pathogen unspecified), fever, headache, infusion-related reactions, neutropenia, anemia, febrile neutropenia, and thrombocytopenia.
Blinatumomab carries a boxed warning alerting patients and health-care professionals that some clinical trial participants had problems with low blood pressure and difficulty breathing (cytokine-release syndrome) at the start of the first treatment, or experienced a short period of difficulty with thinking or other side effects in the nervous system. Serious risks of blinatumomab include infections, effects on the ability to drive and use machines, pancreatitis, and preparation and administration errors—instructions for preparation and administration should be followed closely. There is a risk of serious adverse reactions in pediatric patients due to benzyl alcohol preservative; therefore, the drug prepared with preservative-free saline should be used for patients weighing less than 22 kg.
This new indication for blinatumomab was approved under the accelerated approval pathway, under which the FDA may approve drugs for serious conditions where there is unmet medical need and a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients. Further study in randomized controlled trials is required to verify that achieving undetectable MRD with blinatumomab improves survival or disease-free survival in patients with ALL.
The FDA granted this application Priority Review, and it received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
The FDA granted the approval of blinatumomab to Amgen Inc.
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®.
