Ofatumumab for the treatment of chronic lymphocytic leukemia

Abstract

Ofatumumab is a humanized second-generation monoclonal antibody with the affinity to a transmembrane protein CD20. In in vitro studies, it exhibits higher efficacy towards chronic lymphocytic leukemia (CLL) cells compared to rituximab, and it can be explained by the fact that its epitope on the target CD20 protein is different as it includes a short as well as a long extracellular loop. Ofatumumab is especially effective in the lysis of CD20 low-expressing lymphocytes that are often observed in CLL. Currently, this agent is approved for the treatment of fludarabine- and alemtuzumab-refractory CLL. There are also promising preliminary results of the studies that indicate benefits of ofatumumab not only in patients with bulky/fludarabine-refractory CLL but also in treatment-naive patients with CLL with contraindications to fludarabine and in maintenance treatment.

Real‐world clinical experience in the Connect® chronic lymphocytic leukaemia registry: a prospective cohort study of 1494 patients across 199 US centres

“…As this registry enrolled patients between 2010 and 2014, and enrolment in clinical trials was low (<5%), very few patients were treated with investigational kinase inhibitor therapies. The approval of agents, such as ibrutinib and idelalisib, by the United States Food and Drug Administration has transformed the management of CLL, particularly for patients with relapsed/refractory (R/R) disease, unfavourable prognostic factors, or advanced age (for whom CIT regimens may be too toxic) (Grosicki, ; Morabito et al , ,b; Tucker & Rule, ). Landmark studies that contributed to these approvals and their widespread adoption included randomized comparisons against agents such as chlorambucil, ofatumumab, and rituximab (Byrd et al , ; Furman et al , ; Sharman et al , ; Hillmen et al , ).…”

New Pharmacological Approaches in the Treatment of Oncological Diseases

“…The binding of the "small loop" thus differs from the binding site of the second currently available CD20 antibody rituximab. This explains the higher efficacy towards chronic lymphocytic leukemia (CLL) cells compared to rituximab [24]. In addition, ofatumumab remains longer at the binding place, resulting in a greater activation of the immune system -may be an indication for the particularly high effectiveness of the new drug, even at low levels of CD20 expression, as is the case in CLL.…”