Indication

ARZERRA (ofatumumab) is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab.

The effectiveness of ARZERRA is based on the demonstration of durable objective responses. No data demonstrate an improvement in disease-related symptoms or increased survival with ARZERRA.

Important Safety Information

Infusion Reactions
ARZERRA can cause serious infusion reactions manifesting as bronchospasm, dyspnea, laryngeal edema, pulmonary edema, flushing, hypertension, hypotension, syncope, cardiac ischemia/infarction, back pain, abdominal pain, pyrexia, rash, urticaria, and angioedema. Infusion reactions occur more frequently with the first 2 infusions. Premedicate with acetaminophen, an antihistamine, and a corticosteroid. Interrupt infusion for infusion reactions of any severity. Institute medical management for severe infusion reactions, including angina or other signs and symptoms of myocardial ischemia. In a study of patients with moderate to severe chronic obstructive pulmonary disease, an indication for which ARZERRA is not approved, 2 of 5 patients developed Grade 3 bronchospasm during infusion. Infusion reactions occurred in 44% of patients on the day of the first infusion (300 mg), 29% on the day of the second infusion (2000 mg), and less frequently during subsequent infusions.

Cytopenias
Prolonged (≥1 week) severe neutropenia and thrombocytopenia can occur with ARZERRA. Monitor complete blood counts (CBC) and platelet counts at regular intervals during therapy, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Of 108 patients with normal neutrophil counts at baseline, 45 (42%) developed ≥Grade 3 neutropenia. Nineteen (18%) developed Grade 4 neutropenia. Some patients experienced new onset Grade 4 neutropenia >2 weeks in duration.

Progressive Multifocal Leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML), including fatal PML, can occur with ARZERRA. Consider PML in any patient with new onset of or changes in pre-existing neurological signs or symptoms. Discontinue ARZERRA if PML is suspected, and initiate evaluation for PML, including consultation with a neurologist, brain MRI, and lumbar puncture.

Hepatitis B Reactivation
Hepatitis B reactivation, including fulminant hepatitis and death, occurs with other monoclonal antibodies directed against CD20. Screen patients at high risk of hepatitis B virus (HBV) infection before initiation of ARZERRA. Closely monitor carriers of hepatitis B for clinical and laboratory signs of active HBV infection during treatment with ARZERRA and for 6 to 12 months following the last infusion of ARZERRA. Discontinue ARZERRA in patients who develop viral hepatitis or reactivation of viral hepatitis, and institute appropriate treatment. Insufficient data exist regarding the safety of administration of ARZERRA in patients with active hepatitis.

Intestinal Obstruction
Obstruction of the small intestine can occur in patients receiving ARZERRA. Perform a diagnostic evaluation if obstruction is suspected.

Immunizations
The safety of immunization with live viral vaccines during or following administration of ARZERRA has not been studied. Do not administer live viral vaccines to patients who have recently received ARZERRA. The ability to generate an immune response to any vaccine following administration of ARZERRA has not been studied.

Most Common Adverse Reactions
In the pivotal study (n=154) the most common adverse reactions (≥10%) were neutropenia, followed by pneumonia (23%), pyrexia (20%), cough (19%), diarrhea (18%), anemia (16%), fatigue (15%), dyspnea (14%), rash (14%), nausea (11%), bronchitis (11%), and upper respiratory tract infections (11%).

Most Common Serious Adverse Reactions
In patients who received an infusion of 2000 mg of ARZERRA, the most common serious adverse reactions were infections (including pneumonia and sepsis), neutropenia, and pyrexia.

A total of 108 patients (70%) experienced bacterial, viral, or fungal infections. A total of 45 patients (29%) experienced ≥Grade 3 infections, of which 19 (12%) were fatal. The proportion of fatal infections in the fludarabine- and alemtuzumab-refractory group was 17%.