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.

Keywords:

• chronic lymphocytic leukemia
• efficacy
• guidelines
• monoclonal antibody
• ofatumumab
• recommendations
• safety
• treatment

Financial & competing interests disclosure:

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Ofatumumab is a fully humanized second-generation monoclonal antibody that binds to a unique epitope of the CD20 membrane protein expressed on B cells, including its short and long loop, therefore it is located near the cell membrane and its efficacy is higher.

• Tolerability of treatment with ofatumumab is very good and there was no drug-specific toxicity.

• Currently, this agent is approved for the treatment of fludarabine- and alemtuzumab-refractory chronic lymphocytic leukemia (CLL).

• Based on currently published results of clinical studies there is a hope for a wider use of ofatumumab in clinical practice in CLL. Preliminary results of Phase II and III studies that have been recently published indicate benefits of ofatumumab in patients with bulky/fludarabine-refractory CLL, but above all in treatment-naive patients with CLL with contraindications to fludarabine and in maintenance treatment.

• To improve not only the efficiency but also anti-infective safety of the treatment with ofatumumab, especially when prolonged administration thereof, the regular substitution of fresh frozen plasma in patients with CLL should be considered.

• To minimize the negative impact on the effectiveness of treatment of shaving/trogocytosis mechanisms that accompany by infusions of ofatumumab, research on modifying the method of administration of the drug, taking into account the possibility of subcutaneous or just more frequently administered smaller doses should be considered.

• Combination of ofatumumab with steroids and other immunosuppressive drugs should be recommended for the treatment of patients with CLL with the presence of immune anemia and/or thrombocytopenia.

• In the near future, we should expect studies regarding combined treatment with ofatumumab and new classes of agents that raise special excitement about more effective CLL therapy such as Bruton kinase inhibitors or Bcl-2 inhibitors.