Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns, and opportunities

Author(s): Lorenzo Falchi1;Santosha A. Vardhana1;Gilles A. Salles1
Source: Blood (2023) 141 (5): 467–480
Maem Hussein MD

Dr. Maen Hussein's Thoughts

This is not a trial, but really a very nice review article, too. A good read especially as we may start prescribing those meds locally.

Treatment paradigms for B-cell non-Hodgkin lymphomas (B-NHL) have shifted dramatically in the last 2 decades following the introduction of highly active immunotherapies such as rituximab. Since then, the field has continued to witness tremendous progress with the introduction of newer, more potent immunotherapeutics, including chimeric antigen receptor T-cell therapy, which have received regulatory approval for and currently play a significant role in the treatment of these diseases. Bispecific antibodies (BsAb) are a novel class of off-the-shelf T-cell redirecting drugs and are among the most promising immunotherapeutics for lymphoma today. BsAb may target various cell-surface antigens and exist in different formats. Anti-CD20xCD3 BsAb have demonstrated remarkable single-agent activity in patients with heavily pretreated B-NHL with a manageable toxicity profile dominated by T-cell overactivation syndromes. Much work remains to be done to define the optimal setting in which to deploy these drugs for B-NHL treatment, their ideal combination partners, strategies to minimize toxicity, and, perhaps most importantly, pharmacodynamic biomarkers of response and resistance. In this review, we provide an update on BsAb development in B-NHL, from discovery to clinical applications, highlighting the achievements, limitations, and future directions of the field.

 

Author Affiliations

1Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Durable Responses With Mosunetuzumab in Relapsed/Refractory Indolent and Aggressive B-Cell Non-Hodgkin Lymphomas: Extended Follow-Up of a Phase I/II Study

Mosunetuzumab has an impressive response rate and durability of response in heavily pre-treated patients with B-cell NHL. This was presented at our webinar on August 7, 2024 by the cellular therapy team, slides are available upon request. We have this drug available at select sites within our practice so please contact us if you have a patient in mind.

Read More »

Recent Bendamustine Treatment Before Apheresis Has a Negative Impact on Outcomes in Patients With Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy

This gives more credence to the idea of avoiding bendamustine before CAR T therapy. Patients exposed to bendamustine had about a 20% lower overall response rate (ORR), 50% shorter progression-free survival (PFS) and >50% shorter overall survival (OS) compared to those who were bendamustine naive. Although other factors may also play a role here, these seem to be significant differences and should make it clear that one should not use this drug before pursuing CAR T therapy.

Read More »