The US Food and Drug Administration (US FDA) has granted approval of Amgen's Blincyto (blinatumomab) for the treatment of patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (ALL). This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials. 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 FDA's breakthrough therapy designation and accelerated approval of Blincyto underscores the critical need for new treatment options for patients with relapsed or refractory B-cell precursor ALL, who are often young adults," said Sean E. Harper, MD, executive vice president of research and development at Amgen. "Blincyto is the first clinical and regulatory validation of the BiTE platform, a new and innovative approach that helps the body's own immune system fight cancer."

The Blincyto approval is based on results of Amgen's '211 trial, a phase 2, multicenter, single-arm open-label study. Eligible patients were > 18 years of age with Ph- relapsed or refractory B-cell precursor ALL. Relapsed or refractory was defined as relapsed with first remission duration of < 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 > 10 per cent blasts in bone marrow. Of the 185 patients evaluated in the trial, 41.6 per cent (77/185; 95 per cent CI: 34.4-49.1) achieved complete remission or complete remission with partial hematologic recovery (CR/CRh) within two cycles of treatment with Blincyto, which was the primary endpoint of the study. The majority of responses (81 per cent [62/77]) occurred within the first cycle of treatment. Among patients who achieved CR/CRh, 39 per cent (30/77) went on to HSCT, and 75.3 per cent (58/77 95 per cent CI: 64.2-84.4) achieved minimal residual disease (MRD) response, a measure of eradication of residual disease at the molecular level.

"The approval of Blincyto represents a significant milestone in immunotherapy research, providing clinicians the opportunity to offer a new single-agent therapy to patients fighting this highly aggressive cancer with previously limited options," said Anthony S. Stein, MD, clinical professor, Hematology/Oncology at City of Hope.

Blincyto has a BOXED WARNING in its product label regarding Cytokine Release Syndrome (CRS) and Neurological Toxicities.

Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving Blincyto. Interrupt or discontinune Blincyto as recommended. Neurological toxicities, which may be severe, life-threatening, or fatal, occurred in patients receiving Blincyto. Interrupt or discontinue Blincyto as recommended.

Blincyto is contraindicated to patients with known hypersensitivity to blinatumomab or to any component of the product formulation.

Monitor patients for signs and symptoms of infection and treat appropriately.Advise patients to refrain from driving and engaging in hazardous occupations or activities such as driving, operating heavy or potentially dangerous machinery while Blincyto is being administered.

It is important to strictly follow instructions for preparation (including admixing) and administration to prevent overdose and underdose.The most common adverse reactions (= 20 per cent) were pyrexia (62 per cent), headache (36 per cent), peripheral edema (25 per cent), febrile neutropenia (25 per cent), nausea (25 per cent), hypokalaemia (23 per cent), rash (21 per cent), tremor (20 per cent) and constipation (20 per cent). Serious adverse reactions were reported in 65 per cent of patients. The most common serious adverse reactions (= 2 per cent) 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 Blincyto REMS is to inform healthcare providers of the serious risks of CRS, neurological toxicities, and preparation and administration errors.

Amgen and its subsidiary Onyx Pharmaceuticals, Inc., which will commercialise Blincyto in the US, have announced the availability of Onyx Pharmaceuticals 360 (Onyx 360), to patients receiving Blincyto in the US. Onyx 360 is a comprehensive patient and caregiver support and services programme designed to help patients navigate the treatment journey, including reimbursement and payment support, treatment support and referrals to third-party organisations for day-to-day needs and emotional support.

Blincyto is the first BiTE antibody construct and the first single-agent immunotherapy to be approved by the US Food and Drug Administration (US FDA). Blincyto was granted breakthrough therapy and priority review designations by the FDA, and is now approved in the US for the treatment of Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (ALL).

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 (a type of white blood cell capable of killing other cells perceived as threats) 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). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers.