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Bispecific Antibodies for Relapsed/Refractory DLBCL

Posted: May 02, 2024
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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.

Stay always up-to-date with the latest news about lymphoma. Sign up for our newsletter!

SUBSCRIBE TO DLBCL NEWSLETTER

Sources: 

 

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.

Stay always up-to-date with the latest news about lymphoma. Sign up for our newsletter!

SUBSCRIBE TO DLBCL NEWSLETTER

Sources: 

 

The author Lisa Foster

about the author
Lisa Foster

Lisa Foster is a mom of 3 daughters and 1 perfect grandchild, a puzzle lover, writer and HealthTree advocate. She believes in the mission of the foundation and the team that builds it forward. She calls Houston, Texas home. 

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