Looking ahead to CD3, T-cell engager bispecific antibodies for hematological malignancies

ABSTRACT

Introduction

Since the approval of the bispecific antibody blinatumomab in 2017 for the treatment of acute lymphoblastic leukemia in relapse, the development of numerous bispecific antibody constructs has dramatically expanded in hematologic malignancies. Many have recently received Food Drug Administration and European Medicines Agency approvals in various stages of treatment for lymphomas, leukemias, and multiple myeloma.

Areas covered

The purpose of this review is to provide an overview of bispecific antibody treatment including the mechanisms leading to effector T cells targeting tumor-associated antigens, the treatment indications, efficacies, toxicities, and challenges of the different constructs. A literature search was performed through access to PubMed and clinicaltrials.gov.

Expert opinion

While there has been substantial success in the treatment of NHL, MM, and ALL, there are still hematologic malignancies such as AML where there has been limited progress. It is important to continue to investigate new designs, tumor antigen targets, and further refine where current approved bispecific antibodies fit in terms of sequencing of therapy. Hopefully, with the knowledge gained in recent years and the explosion of these therapies, patients with blood cancers will continue to benefit from these treatments for years to come.

KEYWORDS:

• Hematologic malignancies
• acute lymphoblastic leukemia
• multiple myeloma
• non-Hodgkin lymphoma
• acute myeloid leukemia
• bispecific antibodies

Article highlights

• Most currently approved bispecific antibodies are used in the relapsed setting for NHL and MM.

• Blinatumomab has been shown to be effective in patients with relapsed B-ALL and in patients with or without measurable residual disease after standard induction chemotherapy improving outcomes.

• There are yet to be any promising outcomes in the use of bispecific antibodies in the treatment of AML despite several previous and ongoing investigations.

• There are several advantages and disadvantages that have been discovered during clinical trials with the different bispecific antibody constructs in various blood cancers.

• Toxicities to bispecific antibodies are well described and understood, and the treatment of these has made this therapy tolerable and safe in patients.

• Current studies are underway evaluating sequencing, combinations, and timing of treatment in patients with hematologic malignancies.

Declaration of interest

LG Lum is the co-founder of Transtarget, Inc., a SAB member for Rapa Therapeutics and Tundra Targeted Therapeutics, Inc. LG Lum is the founder of BATs, LLC. LG Lum has multiple patents received and pending related to bispecific antibody-armed T cells. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.