An evaluation of glofitamab, the first fixed-duration bispecific antibody for relapsed or refractory large B-cell lymphomas

ABSTRACT

Introduction

Significant proportion of patients with diffuse large B-cell lymphoma (DLBCL) is refractory or relapse (R/R) after the treatment. The prognosis of this patient cohort remains poor. Novel strategies mainly based on immunotherapy and targeted agents are currently being studied. Glofitamab is novel T-cell-engaging bispecific antibody possessing a 2:1 structure with bivalent CD20 binding. Its safety and efficacy in R/R B-cell non-Hodgkin lymphoma including DLBCL were evaluated in phase I-II NP30179 trial.

Areas covered

The article summarizes the milestones and latest reports on glofitamab development in the field of B-cell lymphoma treatment.

Expert opinion

Recently, phase II part of the NP30179 study and several other reports were published proving glofitamab potential in R/R DLBCL patients. Based on the published data, glofitamab was approved by regulatory authorities worldwide for the monotherapy of R/R DLBCL in conventional time-limited manner. It is readily accessible in case of rapidly progressing disease, and it compares well with other novel treatment options. Its side effects are similar to those of other T-cell-engaging agents and can be mitigated by pretreatment with obinutuzumab or step-up dosing. Its safety profile with manageable toxicities heads the clinical development toward combination strategies and its use in earlier therapeutic phases.

KEYWORDS:

• Bispecific antibody
• T-cell engager
• diffuse large B-cell lymphoma
• immunotherapy
• glofitamab

Article highlights

• Glofitamab, a CD3/CD20 targeting bispecific antibody is a T-cell engager with significant antilymphoma efficacy leading to complete remission in ~ 40% of patients with DLBCL in monotherapy settings.

• Even though the treatment is time-limited, patients reaching CR experience relapses rarely and most of them remain in remission after 2 years.

• The treatment is effective also in DLBCL patient after CAR T-ly therapy failure, and in some of the patients a CAR T-ly re-expansion may occur.

• The current data suggest high efficacy of glofitamab also in other B-NHL histologies, such as follicular lymphoma or mantle cell lymphoma.

• The low myelotoxicity and favorable safety profile with good tolerability allow the use of glofitamab in various combination strategies with different targeted molecules as well as with conventional chemotherapy.

Declaration of interest

K Polgarova reports travel grants and consultancy fees from Novartis, Roche, Gilead, Takeda and Kyowa Kirin. M Trneny reports travel grants and consultancy fees from Novartis, Roche, Gilead, Takeda, Janssen and Kyowa Kirin. 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

A peer reviewer on this manuscript received an honorarium from Expert Opinion on Biological Therapy for their review work. The reviewers have no other relevant financial relationships to disclose.

Company review

Roche provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This manuscript was supported by CUNI Cooperatio Program Hem-Oncol and AZV NU21-03-00411.