On December 3, 2014, the U. S. Food and Drug Administration granted accelerated approval for blinatumomab (BLINCYTO, Amgen Inc.) for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R ALL).
The approval was based on the achievement of durable complete remission (CR) and response with a reduction in minimal residual disease (MRD) to less than 10-4 in a multicenter single-arm trial (Protocol MT103-211) that enrolled 185 patients with R/R ALL. Blinatumomab was administered by continuous infusion for 4 weeks of a 6-week cycle. Up to two cycles were used for induction and three cycles for consolidation.
In Protocol MT103-211, 32% (95% CI, 26% - 40%) of patients with R/R ALL attained CR with 2 cycles of treatment with single-agent blinatumomab, and the response was durable (median 6.7 months; range, 0.46 - 16.5 months). Furthermore, 31% (95% CI, 25%-39%) of the patients in the study had a CR with or without complete hematological recovery but with reduction in MRD to <10-4.
Safety was evaluated in 212 patients with R/R ALL treated with blinatumomab. The most common adverse reactions (greater than or equal to 20%) were pyrexia (62%), headache (36%), peripheral edema (25%), febrile neutropenia (25%), nausea (25%), hypokalemia (23%), rash (21%), tremor (20%), and constipation (20%). A neurological toxicity occurred in approximately 50% of patients and was a frequent reason for interruption of therapy.
Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that activates endogenous T cells when bound to the CD19-expressing target cell. Activation of the immune system results in release of inflammatory cytokines. Cytokine release syndrome, including life-threatening or fatal events, was reported in 11% of the patients. A Boxed Warning regarding cytokine release syndrome and neurological toxicities is provided in the product labeling. In addition, FDA approved blinatumomab with a Risk Evaluation and Mitigation Strategy (REMS) which consists of a communication plan to inform health care providers about the serious risks and the potential for preparation and administration errors.
For patients weighing at least 45 kg, the recommended dose and schedule for blinatumomab is 9 mcg/day on days 1-7 and at 28 mcg/day on days 8-28 of the first 42-day cycle, and 28 mcg/day on days 1-28 in later cycles.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125557lbl.pdf
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).