Bispecific antibodies in the treatment of relapsed/refractory large B-cell lymphoma

ABSTRACT

Introduction

The management of relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) has witnessed dramatic changes in the recent past. Despite the availability of multiple novel immunotherapies in R/R setting, there remains an unmet need for off-the-shelf therapies, particularly in patients with primary refractory, multiply relapsed disease or those experiencing cellular immunotherapy failure. To harness the power of the T-cell mediated immunity, a novel class of drugs called bispecific antibodies (BsAbs) have been developed. These BsAbs are currently under investigation both in frontline and R/R setting and hold the potential to revolutionize the management of LBCL.

Areas covered

This review article summarizes the currently available BsAbs, their mode of action, efficacy, and safety data for untreated and R/R LBCL. In addition, the role of these BsAbs in combination with currently available chemoimmunotherapy regimens is also discussed.

Expert opinion

Two BsAbs have secured FDA approval for R/R LBCL, with expected approval of more BsAbs (including in earlier treatment lines). These drugs provide a highly efficacious and relatively safe treatment option for patients with highly pretreated disease including relapse after cellular immunotherapies. In addition, these BsAbs provide a platform for chemotherapy-free regimen for older/frail patients.

KEYWORDS:

• Bispecific antibody
• glofitamab
• epcpritamab
• mosunetuzumab
• odronextamab
• trispecific antibodies

Article highlights

• Currently, two BsAbs, i.e. glofitamab and epcoritamab, have been approved by FDA for the treatment of R/R DLBCL after two prior treatments. These anti-CD20 X CD3 antibodies have demonstrated durable response in heavily pre-treated patients including patients who relapse after CAR T-cell therapy.

• Several other BsAbs are currently under investigation and have demonstrated excellent efficacy and safety profiles in this patient population.

• The BsAbs have also exhibited an excellent safety profile and improvement in efficacy when used in combination with other chemoimmunotherapy regimens.

• Use of these BsAbs in the first line setting with currently available chemoimmunotherapy is being evaluated in several clinical trials and the preliminary data are encouraging.

• Several trispecific antibodies are also currently under investigation for patients with R/R LBCL.

• There are several limitations of BsAbs including long-term immunosuppression leading to a high risk of infections and lack of long-term data for the duration of response.

Declaration of interest

M Hamadani reports: Consultancy: Incyte Corporation; ADC Therapeutics; Pharmacyclics, Omeros, Genmab, Morphosys, Kadmon, Kite, Novartis, Abbvie, Legend, Gamida Cell, SeaGen, Caribou, CRISPR, Autolous Speaker’s Bureau: Sanofi Genzyme, AstraZeneca, BeiGene, ADC Therapeutics. 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.