A submission has been made for ofatumumab to treat patients whose chronic lymphocytic leukaemia (CLL) is refractory to previous therapies. If approved, ofatumumab would be the first anti-CD20 monoclonal antibody available for this patient population.

Ofatumumab is an investigational monoclonal antibody that targets a membrane-proximal, small loop epitope on the CD20 molecule on B-cells.¹ This epitope is different from the binding sites targeted by other CD20 antibodies currently available.² The CD20 molecule is a key target in CLL therapy because it is highly expressed in most B-cell malignancies.³

The final analysis from the international trial of ofatumumab in patients with fludarabine and alemtuzumab (FA-ref) or refractory to fludarabine with bulky (>5 cm) lymphadenopathy (BF-ref) CLL was presented at ASH 2010.⁴

Patients received 8 weekly doses of ofatumumab followed by 4 monthly doses (dose 1, 300 mg; doses 2–12, 2000 mg). Premedication included acetaminophen, antihistamine and glucocorticoid. The overall response rate was 51% and 44% for the FA-ref group and BF-ref group, respectively. Infusion-related adverse events, which were grade 1-2 events in 95% of patients, occurred in 63% of patients. These primarily occurred during doses 1 and 2, and diminished with subsequent doses. No fatal reactions were reported.

The most common (≥5% of all patients) grade ≥3 adverse events (AEs) that occurred from start of treatment until 30 days after the last infusion were infections (24%), neutropenia (12%) and anaemia (5%). The most common grade ≥3 infection was pneumonia (8% of patients). Fatal infections occurred in 8% of patients (13% in FA-ref; 5% in BF-ref groups). Grade 3-4 thrombocytopenia occurred in 8 patients (4%), febrile neutropenia in 4 patients (2%) and autoimmune haemolytic anaemia in 2 patients (1%). Early death (within 8 weeks from start of treatment) occurred in 5 patients (5%) in the FA-ref group (infections, n=5) and 4 patients (4%) in the BF-ref group (infections, n=2; myocardial infarction, n=1; pulmonary oedema, n=1).

The investigators of the study concluded that the efficacy and safety of ofatumumab monotherapy in this heavily pretreated patient population with FA-ref and BF-ref CLL was clearly demonstrated.

References 

1. Hagenbeek A, Gadeberg O, et al. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood. 2008;111:5486-5495.

2. Teeling JL, Mackus, W,J., et al. The Biological Activity of Human CD20 Monoclonal Antibodies Is Linked to Unique Epitopes on CD20. J Immunol. 2006;177:362-371.

3. Glennie MJ, French RR, et al. Mechanisms of killing by anti-CD20 monoclonal antibodies. Molecular Immunology.2007;44(16):3823-3837.

4. WG Wierda, TJ Kipps, J Mayer et al. Final Analysis From the International Trial of Single-Agent Ofatumumab In Patients with Fludarabine-Refractory Chronic Lymphocytic Leukemia. Abstract 921. Presented at 52nd ASH, Orlando, FL, December 4-7, 2010.