Ofatumumab in advanced stage chronic lymphocytic leukaemia: results of the UK named patient compassionate use programme.
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Ofatumumab in advanced stage chronic lymphocytic leukaemia: results of the UK named patient compassionate use programme.
Article first published online: 12 MAY 2011
We report our ‘real life’ experience of the use of Ofatumumab in chronic lymphocytic leukaemia (CLL) in the UK compassionate use programme. In addition to patients with bulky fludarabine refractory (BF ref) disease (n = 12) or fludarabine and alemtuzumab refractory (FA ref) disease (n = 4), patients unsuitable for alemtuzumab were included (n = 6). 91% of transfusion dependent patients became transfusion independent. The overall response rate (ORR) was 48% (3/27 clinical CR; 10/27 PR). 4/6 patients with TP53 deletion/mutations responded to Ofatumumab. This is the first series of UK patients confirming that single agent Ofatumumab has efficacy in relapsed refractory CLL and will complement on-going clinical studies.
Although thought to be an indolent disease of the elderly, a significant number of patients with chronic lymphocytic leukaemia (CLL) develop chemotherapy resistance and die from bone marrow failure and infectious complications. Ofatumumab (HuMax-CD20) is a fully humanized anti-CD20 monoclonal antibody with promising activity in B-cell disorders including CLL. It binds to a different epitope to Rituximab and is thought to confer greater complement-mediated cellular cytotoxicity with some additional antibody-dependent cellular cytotoxicity (Cheson, 2010). A recent interim analysis of the first 138 patients entered into the single arm Phase II study Hx CD20 406, evaluated its safety and efficacy in BF ref or FA ref disease (Wierda et al, 2010). Patients unsuitable for alemtuzumab were excluded. The overall response rate (ORR) was 58% in the FA ref group and 47% in the BF ref group. Perhaps the most significant improvement was in overall survival, which was 13·7 and 15·4 months in the FA ref and BF ref responder groups respectively, compared to 9·8 and 10·2 months in non-responders.
The present analysis included patients recruited into the subsequent UK compassionate use programme by five centres after informed consent, which specified that Ofatumumab was not licensed in the UK, was obtained. Twenty-eight patients were screened but only 27 patients received treatment as one patient died before treatment was commenced. Cytogenetic data was available on 24 patients.
Ofatumumab [GlaxoSmithKline (GSK), Uxbridge, UK] was given weekly for eight infusions and then monthly to complete 12 infusions. The first infusion was given at a dose of 300 mg with all subsequent doses being 2000 mg. Adverse events were communicated to GSK. Response was evaluated clinically and by blood counts according to the International Workshop on Chronic Lymphocytic Leukemia guidelines (Hallek et al, 2008). Improvement of peripheral blood cytopenias and reduction in red cell and platelet transfusion requirements were recorded.
A total of 27 patients with a median age of 65 (range 48–83) years were tre
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