Do DLBCL Patients Experience Brain-Related Side Effects from Bispecific Antibodies?

Bispecific antibodies for the treatment of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma are showing potential to be a gentler, yet effective, alternative to other types of immunotherapies such as CAR T-cell therapy, particularly in reducing the incidence and severity of brain-related side effects. 

What Are Bispecific Antibodies? 

Bispecific antibodies are a type of cancer treatment that helps enhance the immune system’s response to attack cancer cells. They work by attaching to two surface proteins, one on the surface of cancer-killing T-cells and the other on the cancer cell. This binding allows the bispecific antibody to act as a bridge, bringing the T-cell close enough to attack the cancer cell. 

The FDA-approved bispecific antibodies as third-line therapies are epcoritamab (Epkinly) and glofitamab (Columvi) for DLBCL and mosunetuzumab (Lunsumio) for follicular lymphoma. 

Do Bispecific Antibodies Have Fewer Brain-Related Side Effects Than CAR T-Cell Therapy? 

While revolutionary, CAR T-cell therapy has been associated with a side effect called immune effector cell-associated neurologic syndrome (ICANS), characterized by brain symptoms such as confusion, difficulty writing, tremors, lethargy, difficulty concentrating, and, in rare cases, seizures. Up to 48.7% of patients treated with CAR T-cell therapy experience some level of ICANS. 

Most non-Hodgkin lymphoma patients treated with bispecific antibodies experience different brain-related side effects than ICANS, such as mild dizziness and headache. The percentage of these patients who do experience similar ICANS symptoms is much less than CAR T-cell therapy, between 1% and 8%. 

How are Brain-Related Side Effects from Bispecific Antibodies Managed? 

Managing bispecific antibody-related brain side effects typically doesn't require routine brain testing for patients who are not showing symptoms. However, awareness and vigilance are crucial. Patients and their caregivers should be educated about the symptoms of brain-related side effects by their healthcare provider and advised to monitor for any changes.

Should symptoms arise, your healthcare team may provide supportive medicines, conduct imaging tests like CT scans or MRIs, consult with a neurologist (brain doctor), and, in severe cases, admit you to the hospital for closer monitoring. 

In conclusion, bispecific antibodies present a promising therapeutic option for treating diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma, providing a gentler alternative to CAR T-cell therapy with a significantly reduced risk of severe brain-related side effects. With FDA approval for use as third-line therapies, these treatments offer an effective bridge between the immune system's T-cells and cancer cells, enhancing targeted attacks with fewer occurrences of severe neurologic complications like ICANS. Ongoing vigilance and management strategies are essential for addressing milder brain side effects, ensuring patient safety, and improving outcomes.

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Sources

• Consensus recommendations on the management of toxicity associated with CD3×CD20 bispecific antibody therapy
• NCCN Patient Guidelines Follicular Lymphoma 
• NCCN Patient Guidelines Diffuse Large B-cell Lymphoma 
• Forecasting immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor t-cell therapy