Diffuse large B-cell lymphoma (DLBCL) is a fast-growing type of non-Hodgkin lymphoma, a significant cancer in adults. When DLBCL relapses or doesn't respond to treatment (refractory), new options are crucial. Bispecific antibodies offer a promising and innovative approach in this scenario.

Understanding Bispecific Antibodies

• Engineered Soldiers: Bispecific antibodies are a novel class of drugs that act as "off-the-shelf" T-cell redirectors. Imagine them as engineered soldiers that recognize and attack cancer cells.
• Dual Targeting: Unlike traditional antibodies, bispecific antibodies can bind to two different targets simultaneously. One target is usually an antigen (protein) on the surface of DLBCL cells. The other target is a molecule on T cells, the body's natural immune system warriors.
• Bringing Together the Forces: By binding to both targets, bispecific antibodies bring T cells into close proximity with cancer cells. This activates the T cells to attack and destroy the DLBCL cells.

Managing Bispecific Antibody Therapy

Bispecific antibody therapy requires careful management through two phases:

• Early Phase: Close monitoring is crucial for potential side effects, including:
  • Cytokine Release Syndrome (CRS): This can cause fever, chills, and fatigue, mimicking an infection.
  • Neurotoxicity: This refers to potential nervous system side effects like headache, confusion, or difficulty walking.
  • Tumor Flare: Sometimes, DLBCL cells may appear to increase initially before responding to treatment. This doesn't necessarily indicate treatment failure.
• Maintenance Phase: The focus here is on preventing infections, a potential risk associated with some bispecific therapies.

Approved Bispecific Antibodies for DLBCL

• Glofitamab (COLUMVI): This is for patients with relapsed/refractory DLBCL. Common side effects include muscle and bone pain, rash, and fatigue. 
• Epcoritamab (EPKINLY): This bispecific T-cell engager (BiTE) is also FDA-approved in May 2023 for patients with relapsed/refractory DLBCL not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B -cell lymphoma (HGBCL).

Other Promising Bispecific Antibodies in Research

• Monsunetuzumab: Studies suggest it starts attacking cancer cells quickly but may require combination therapy for long-term benefits.
• Blinatumomab: This therapy targets the CD19 protein on cancer cells and is administered in cycles with steroids to manage potential side effects.
• Odronextamab: This investigational bispecific antibody targets CD20 on cancer cells and CD3 on T cells. Early clinical trials have promise, and it is currently undergoing regulatory review for DLBCL treatment.

The Future of Bispecific Antibodies

Bispecific antibodies represent a significant advancement in DLBCL treatment. They offer a new way to harness the body's immune system to fight cancer. As research progresses, these therapies hold the potential to improve outcomes for DLBCL patients.

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Sources: 

• FDA Hematologic Malignancies Approval Notifications
• Bi- and Tri-specific antibodies in non-Hodgkin lymphoma: current data and perspectives