Treatment of chronic lymphocytic leukemia with monoclonal antibodies, where are we heading?

Abstract

Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the western world and monoclonal antibodies (mAbs) are important part of CLL treatment. The goal of this article was to summarize current literature on the position of mAbs in CLL treatment and to mention factors influencing effectiveness of mAbs in CLL. Several new mAbs have been developed and investigated in CLL over the past few years. Mainly anti-CD20 monoclonal antibodies are still used routinely in CLL therapy. Unfortunately, the clinical application of mAbs needs to be further improved. Novel combinations and sequences of mAbs with other compounds need to be studied in clinical trials in order to increase overall response rate and prolong remission duration. Mechanisms of action of mAbs or mechanisms of resistance to mAbs have to be also investigated to predict effectiveness of mAb in particular patient.

Keywords:

• CD20
• CD52
• chronic lymphocytic leukemia
• monoclonal antibodies
• resistance
• therapy

Financial & competing interests disclosure

Supported in part by Research Grants MSMT CR CZ.1.05/1.1.00/02.0068 (CEITEC), AZV 15-33561A, and by the Czech Leukemia Study Group – for Life. The authors have no other 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 apart from those disclosed.

Key issues

• mAbs are and will be an important part of CLL treatment.

• Novel mAbs are under evaluation for safety and efficacy in patients with CLL.

• Anti-CD20 mAbs will remain the most important mAbs in the CLL therapy.

• Unfortunately, alemtuzumab will be displaced by other mAbs, in spite alemtuzumab being one of the most effective mAbs in the CLL treatment.

• In general, combinations of mAbs with other agents are more effective than mAbs in monotherapy.

• Novel combinations and sequences of mAbs with other compounds need to be studied further in clinical trials in order to increase treatment efficacy.

• In the near future, novel agents (BCR signaling inhibitors, apoptosis inducers) will be main partners of mAbs in CLL therapy.

• Mechanisms of the action of mAbs and mechanisms of resistance (antigen density regulation, complement inhibitory molecules, effector cells) to mAbs are not well understood and need to be intensively investigated to predict the effectiveness of mAb in a particular patient.

• Without better understanding of mechanisms of mAb action and resistance, no further improvement of CLL treatment with these agents will be possible.