FDA grants accelerated approval to Amgen’s MRD-positive ALL treatment

The US Food and Drug Administration (FDA) has granted accelerated approval to Amgen’s Blincyto (blinatumomab) to treat adults and children with B-cell precursor acute lymphoblastic leukaemia (ALL) who are in remission but still have minimal residual disease (MRD).

“This is the first FDA-approved treatment for patients with MRD-positive ALL,” said Dr Richard Pazdur, 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 leukaemia cells may help keep the cancer in remission longer. We look forward to furthering our understanding about the reduction in MRD after treatment with Blincyto. Studies are being conducted to assess how Blincyto affects long-term survival outcomes in patients with MRD.”

“Until today, no therapy has been satisfactory in eradicating MRD or approved specifically to treat this high-risk patient population,” added Dr David M. Reese, senior vice president of Translational Sciences and Oncology at Amgen. “This approval not only supports the use of Blincyto earlier in the ALL treatment continuum, but represents a paradigm shift in the management of ALL.”

“The detection of remaining cancer cells after a complete remission is the strongest prognostic factor for relapse in patients with ALL. It’s critical to test for and know your patients’ MRD status, because we know that treating to MRD-negativity will help to obtain better possible clinical outcomes for patients,” explained Dr Elias Jabbour, associate professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston. “In the BLAST study, blinatumomab led to no detectable cancer cells in approximately 80% of patients with MRD-positive ALL. This approval provides a much-needed treatment option to destroy the remaining detectable traces of leukaemia.”

Blincyto functions through attaching itself to the CD19 protein, that exist on leukaemia cells, and CD3 protein found on certain immune system cells. As the immune cells are then closer to the leukaemia cells it makes it easier for them to attack the disease.

The FDA first approved Blincyto under accelerated approval in December 2014 for the treatment of Philadelphia chromosome (Ph)-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.

This new indication for Blincyto 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 Blincyto improves survival or disease-free survival in patients with ALL.

The application was granted as a priority review and has received orphan drug designation by the FDA.