Anti-CD20 monoclonal antibody targets CD20 cell surface marker on the majority of malignant B cells.
Ofatumumab targets CD20 induces cell death through antibody-dependent cell-mediated toxicity, complement-dependent cytotoxicity, and apoptosis.
Trade name Arzerra.
Phase I/II study of 33 patients with relapsed or refractory B cell CLL yielded a response rate of 50%.
Associated with high infection rate of 51%.
Approved for CLL that has not responded to fludarabine and alemtuzumab.
Binds to the CD 20 antigen at a unique epitope and increase his complement mediated cytotoxicity.
Has in vitro complement defended cytotoxicity in ritux imab refractory cells, higher antibody-dependent cytotoxicity toxicity than rituximab and in vivo efficacy in rituximab refractory CLL.
Active in patients with bulky disease refractory to fludrabine.
Active in patient that failed prior rituximab anti-CD20 therapy.
In rituximab refractory follicular lymphoma patients the response rate is only 10%, suggesting this agent cannot overcome resistance to rituximab (Hagenbeek A et al).
It may be associated with progressive multifocal leukoencephalopathy, and reactivation of hepatitis B.
Most common adverse reactions include neutropenia, pneumonia, fever, cough, diarrhea, fatigue, dyspnea, anemia, nausea, rash, and bronchitis.
Ofatumumab plus chlorambucil approved for previously untreated patients with chronic lymphocytic leukemia (CLL) who are considered inappropriate for treatment with fludarabine therapy, based on an improvement in progression-free survival (PFS) in a phase III trial.
In the trial, labeled COMPLEMENT 1: the combination of the anti-CD20 monoclonal antibody ofatumumab and chlorambucil demonstrated a 9.3-month improvement in PFS compared with chlorambucil alone.
The overall response rate (ORR) with the combination was 82% versus 69% with chlorambucil alone.
The COMPLEMENT 1 study enrolled 447 patients with CLL who were considered inappropriate for fludarabine-based therapy due to advanced age and/or comorbidities.
Chlorambucil was administered orally at 10mg/m2 on days 1 through 7 of each 28-day cycle.
Ofatumumab was administered intravenously at 300-mg on day 1 followed by 1000-mg on day 8 and day 1 of subsequent cycles.
The median PFS by independent review was 22.4 months with ofatumumab plus chlorambucil compared with 13.1 months for chlorambucil alone
Overall response rate was 82% versus 69% with a complete response rate of 12% versus 1%, for ofatumumab plus chlorambucil compared with chlorambucil alone, respectively.
The most common grade 3/4 toxicity was neutropenia, which occurred in 26% of patients treated with ofatumumab compared with 14% for chlorambucil alone.
Grade 3/4 infusion-related adverse events were reported in 10% of patients.
Ofatumumab targets CD20 induces cell death through antibody-dependent cell-mediated toxicity, complement-dependent cytotoxicity, and apoptosis.