The FDA ( Food and Drug Administration ) has granted approval of Blincyto ( Blinatumomab ) for the treatment of patients with Philadelphia chromosome-negative ( Ph- ) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
This indication is approved under accelerated approval.
With this approval, Blincyto becomes the first FDA-approved bispecific CD19-directed CD3 T-cell engager ( BiTE ) antibody construct product, and the first single-agent immunotherapy to be approved for the treatment of patients with Ph- relapsed or refractory B-cell precursor ALL, a rare and rapidly progressing cancer of the blood and bone marrow.
The Blincyto approval is based on results of Amgen's '211 trial, a phase 2, multicenter, single-arm open-label study. Eligible patients were greater than or equal to18 years of age with Ph- relapsed or refractory B-cell precursor ALL.
Relapsed or refractory was defined as relapsed with first remission duration of greater than or equal to 12 months in the first salvage, or relapsed or refractory after first salvage therapy, or relapsed within 12 months of allogeneic hematopoietic stem cell transplantation ( HSCT ), and had greater than or equal to 10% blasts in bone marrow.
Of the 185 patients evaluated in the trial, 41.6% ( 77/185; 95% CI: 34.4-49.1 ) achieved complete remission or complete remission with partial hematologic recovery ( CR/CRh ) within two cycles of treatment with Blinatumomab, which was the primary endpoint of the study. T
he majority of responses ( 81% [ 62/77 ] ) occurred within the first cycle of treatment. Among patients who achieved CR/CRh, 39% ( 30/77 ) went on to HSCT, and 75.3% ( 58/77 95% CI: 64.2-84.4 ) achieved minimal residual disease ( MRD ) response, a measure of eradication of residual disease at the molecular level.
Blincyto has a Boxed warning in its product label regarding cytokine release syndrome ( CRS ) and neurological toxicities.
Blincyto is contraindicated to patients with known hypersensitivity to Blinatumomab or to any component of the product formulation.
The most common adverse reactions ( greater than or equal to 20% ) were pyrexia ( 62% ), headache ( 36% ), peripheral edema ( 25% ), febrile neutropenia ( 25% ), nausea ( 25% ), hypokalaemia ( 23% ), rash ( 21% ), tremor ( 20% ) and constipation ( 20% ).
Serious adverse reactions were reported in 65% of patients. The most common serious adverse reactions ( greater than or equal to 2% ) included febrile neutropenia, pyrexia, pneumonia, sepsis, neutropenia, device-related infection, tremor, encephalopathy, infection, overdose, confusion, Staphylococcal bacteremia and headache.
The FDA has also approved a risk evaluation and mitigation strategy ( REMS ) for Blincyto. The purpose of the REMS is to inform healthcare providers of the serious risks of cytokine release syndrome, neurological toxicities, and preparation and administration errors.
Bispecific T cell engager ( BiTE ) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body's immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells to cancer cells.
BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die ( apoptosis ). ( Xagena )
Source: Amgen, 2014