Ublituximab for the treatment of CD20 positive B-cell malignancies

ABSTRACT

Introduction: Non-Hodgkin lymphoma (NHL) is the most common adult hematologic malignancy. Conventional methods of treatment are chemotherapy and radiation, which were associated with toxicities and lack of specificity. Potential cell surface targets for treatment of B-cell NHL (B-NHL) include CD19, CD20, and CD22 which are highly expressed on malignant B-cells. The development of monoclonal antibody (mAb) therapy directed against CD20 had the most clinical impact in the treatment of B-NHL. Early clinical trials with rituximab (RTX), the first chimeric mAb against CD20, showed efficacy and minimal toxicities. RTX was later approved as first line in combination with CHOP chemotherapy for Diffuse Large B-NHL (DLBCL). The emergence of resistance to RTX prompted the development of the next-generation of mAbs targeting CD20 (e.g. obinituzumab, ofatumumab), and includes ublituximab (Ub), with higher complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) against malignant B-cells.

Areas covered: Herein, we discuss clinical trials of Ub, highlighting efficacy, tolerability and an expert opinion on drug development in B-NHL. A pubmed search was conducted to evaluate all Ub clinical trials.

Expert opinion: Ub demonstrated efficacy in patients with high-risk CLL and B-NHL in both first line, subsequent lines, and in rituximab refractory patients.

KEYWORDS:

• Ublituximab
• high-risk
• CLL
• NHL

Box 1. Drug summary box.

Declaration of Interest

The authors have 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. A reviewer on this manuscript disclosed receiving research funding and honoraria from Chugai Pharma, and honoraria from Zenyaku Kogyo. A second reviewer on this manuscript disclosed receiving research funding from Roche for studies on CD20 antibody constructs.

Additional information

Funding

This paper is not funded