On March 29, 2018, the United States Food and Drug Administration (USFDA) granted accelerated approval to Blincyto (blinatumomab) to treat adults and children with B-cell precursor acute lymphoblastic leukemia (ALL) who are in remission but still have minimal residual disease (MRD)49. MRD refers to the presence of cancer cells even below a microscopic level. MRD presence in patients who have achieved remission after initial treatment for this type of ALL, signifies an increased risk of relapse.
Blincyto is the first-and-only FDA-approved therapy for Minimal Residual Disease. Detection of remaining cancer cells after complete remission is the strongest prognostic factor for relapse in patients with Acute Lymphoblastic Leukemia50.
Accelerated approval is based on data from the Phase 2 BLAST Study, the largest prospective trial in Minimal Residual Disease-Positive Acute Lymphoblastic Leukemia. The efficacy of Blincyto 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 one cancer cell in 10,000 cells after one cycle of Blincyto treatment, in addition to the length of time that the patients remained alive and in remission (hematological 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.
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 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 Blincyto to Amgen Inc.
About B-cell precursor acute lymphoblastic leukemia (ALL)
ALL is a rare and rapidly progressing cancer of the blood and bone marrow that occurs in both adults and children. Nearly 50 percent of adult patients and 25 percent of pediatric patients with B-cell ALL eventually relapse or are refractory to treatment. Poor outcomes have been observed in patients who relapse after achieving a complete response but have persistent MRD (disease that remains at the molecular level after treatment). Five-year OS rates are as high as 75 percent for patients that achieve MRD-negative status, compared with 33 percent among patients that remain MRD-positive. In pediatric patients, MRD-positive status after treatment is associated with a 15-times higher risk of relapse compared with those with undetectable residual disease.
The National Cancer Institute estimates that approximately 5,960 people in the United States will be diagnosed with ALL this year and approximately 1,470 will die from the disease.
About Blincyto:
BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE®) immunotherapy that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells. BLINCYTO was granted breakthrough therapy and priority review designations by the FDA in 2014, and is now fully approved in the U.S. for the treatment of relapsed or refractory B-cell precursor ALL in adults and children. BLINCYTO is now also approved under accelerated approval for the treatment of adults and children with B-cell precursor ALL in first or second complete remission with MRD greater than or equal to 0.1 percent. This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival (RFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
In November 2015, BLINCYTO was granted conditional marketing authorization in the European Union for the treatment of adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor ALL. Additional regulatory applications for BLINCYTO are underway and have been submitted to health authorities worldwide.
Footnotes
49. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm603151.htm
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