Blinatumomab

Neutropenia and neutropenic fever, including life-threatening episodes, have been reported. Monitor blood counts throughout therapy; may require therapy interruption if prolonged neutropenia occurs. Anemia and thrombocytopenia may also occur.

Cytokine release syndrome (CRS), which may be life-threatening or fatal, has occurred. Interrupt or discontinue therapy as recommended. Infusion reactions have also occurred, and may be difficult to distinguish from CRS. CRS symptoms may include pyrexia, headache, nausea, weakness, hypotension, increased transaminases, and elevated total bilirubin. In some patients, disseminated intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic histiocytosis/macrophage activation syndrome (MAS) have been reported in the setting of CRS. Monitor closely for signs/symptoms of these conditions; may require therapy interruption or discontinuation. CRS which was life-threatening or fatal occurred rarely. The highest cytokine elevation was observed in the first 2 days following the start of infusion. In 1 study, patients with a high tumor burden (≥50% leukemic blasts or >15,000/mm3 peripheral blood leukemic blast counts), or elevated lactate dehydrogenase were pre-treated with dexamethasone (10 to 24 mg/m2/day for up to 5 days and concluding 3 days prior to initiating blinatumomab) to reduce the incidence of severe CRS (Topp 2015). Tocilizumab may be considered in the management of severe or life-threatening cytokine release syndrome associated with bi-specific T-cell engaging (BiTE) therapy (Lee 2014; Maude 2014).

Transient increases in liver enzymes (associated both with and without CRS) may occur during therapy. In patients with ALL, the median time to enzyme elevation was 3 to 19 days; grade 3 or higher elevations were observed in a small percentage of patients. Monitor ALT, AST, GGT, and total bilirubin at baseline and during treatment. Interrupt therapy if transaminases are >5 times ULN or if bilirubin is >3 times ULN.

Serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-related infections have been reported in approximately one-fourth of patients with ALL in clinical trials (may be life-threatening or fatal). Consider prophylactic antibiotics if appropriate, and monitor closely for signs/symptoms of infection. Treat promptly if infection occurs.

Leukoencephalopathy (as seen on MRI) has been reported, particularly in those patients who received prior treatment with cranial irradiation and antileukemia chemotherapy (eg, high-dose methotrexate, intrathecal cytarabine).

Neurological toxicities, which may be severe, life-threatening, or fatal, have occurred. Interrupt or discontinue therapy as recommended. Neurotoxicity has occurred in almost two-thirds of patients with ALL in clinical trials. The median time to onset was within the first 2 weeks of therapy. Common neurological symptoms include headache and tremor (symptoms may differ in children • Pancreatitis: Fatal cases of pancreatitis in patients receiving blinatumomab plus dexamethasone have been reported in the postmarketing setting. Monitor for signs/symptoms of pancreatitis; may require therapy interruption or discontinuation.

Life-threatening or fatal tumor lysis syndrome (TLS) has been observed. Administer measures to prevent TLS (eg, pretreatment nontoxic cytoreduction and hydration during treatment). Monitor for signs/symptoms of TLS (eg, acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, and/or hyperphosphatemia); may require treatment interruption or discontinuation. Concomitant drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to blinatumomab initiation, during treatment, and until immune system recovery following the last cycle of therapy. Special populations:

Elderly patients experienced an increased rate of neurotoxicity (including cognitive disorder), encephalopathy, confusion, and serious infections as compared to patients • Pediatric: Pediatric patients experienced an increased rate of anemia, thrombocytopenia, vomiting, pyrexia, and hypertension as compared to adult patients. While the incidence of neurologic toxicities in patients Dosage form specific issues:

Diluent may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling. Due to the addition of bacteriostatic saline, the 7-day infusion bags of blinatumomab contain benzyl alcohol and are not recommended for use in patients weighing • Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling. Other warnings/precautions:

Preparation and administration errors have occurred. Do not flush infusion line, particularly when changing infusion bags or at completion of infusion; may result in overdose and complications. IV bag contains overfill and volume will be more than the volume administered to the patient to account for IV line priming and to ensure that the full dose is administered. Follow preparation and administration instructions carefully. Refer to manufacturer labeling for further information.