By Emma Hitt, PhD
SAN FRANCISCO -- December 11, 2008 - Ofatumumab monotherapy is active in patients with double-refractory (DR) or bulky fludarabine-refractory (BFR) chronic lymphocytic leukaemia (CLL), according to findings from a planned interim analysis of an international study.
Lead author Anders Osterborg, MD, PhD, Department of Hematology, Karolinska Hospital, Stockholm, Sweden, and colleagues presented their findings here on December 8 at the American Society of Hematology (ASH) 50th Annual Meeting and Exposition.
Prognosis is poor for patients with CLL that is refractory to fludarabine and alemtuzumab and for patients with bulky lymphadenopathy (>5 cm) that is refractory to fludarabine. Dr. Osterborg and colleagues evaluated ofatumumab in this setting. Ofatumumab is a human monoclonal antibody targeting a unique small-loop epitope on CD20.
The researchers enrolled 59 patients with DR and 79 with BFR and treated them with 8 weekly infusions of ofatumumab followed by 4 monthly infusions (initial dose, 300 mg; subsequent 11 doses, 2,000 mg). Of these patients, 54% received all 12 infusions and 90% received at least 8 infusions.
Response rate was 58% for the DR group and 47% for the BFR groups. One complete response was observed in the BFR group and the remaining responses in both groups were partial responses. Stable disease was achieved in 31% of the DR group and 41% of the BFR group.
Median time to response in both groups was 1.8 months. Median duration of response was 7.1 months and 5.6 months in the DR and BFR groups, respectively. Response at week 12 was significantly correlated with longer survival for both groups.
Infusion-related adverse events occurred with the first infusion in about 46% of patients in the DR group and 39% of the BFR group but decreased in frequency with subsequent treatments. Grade 3/4 haematological events included neutropenia (10% and 10%, respectively) and anaemia (8% and 4%, respectively). Two patients died from sepsis, 2 from pneumonia, and 1 from myocardial infarction.
Response was independent of prior rituximab treatment, age, Rai stage, and number of prior regimens. Responses were observed in the groups with 17p and 11q deletions, which are known to have poor prognosis.
"This monoclonal antibody potentially represents an active treatment option with clinical benefit for patients with very poor prognosis who have exhausted standard treatment options," the authors concluded.
Funding for this study was provided by Genmab.
[Presentation title: Ofatumumab (HuMax-CD20), a Novel CD20 Monoclonal Antibody, Is an Active Treatment for Patients With CLL Refractory to Both Fludarabine and Alemtuzumab or Bulky Fludarabine-Refractory Disease: Results From the Planned Interim Analysis of an International Pivotal Trial. Abstract 328]
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