Bispecific Antibodies for CLL Webinar

On May 13th, as part of HealthTree’s CLL Webinar Program, CLL specialist Dr. Adam Kittai from the Icahn School of Medicine at Mount Sinai shared an enlightening presentation on the potential of bispecific antibodies in treating chronic lymphocytic leukemia (CLL). Watch the event's recording below or read the summary. 

How Do Bispecific Antibodies Work? 

You may be familiar with monoclonal antibodies used in CLL treatment, such as rituximab (Rituxan) and obinutuzumab (Gazyva). Monoclonal antibodies target one protein on the surface of cancerous B-cells like CLL, called CD20. Binding to this surface protein signals the immune system to target and destroy cancer cells. 

Bispecific antibodies attach to two targets. One is the CD20 surface protein on CLL cells, and the second is a surface protein on cancer-killing T-cells. By binding to both targets, the bispecific antibodies act as a bridge, connecting the T-cells to the cancer cell, thereby allowing the T-cells to attack the cancer cell. 

This mechanism of action is helpful as T-cells often have difficulty finding and killing CLL cells on their own. 

Are Bispecific Antibodies FDA-Approved for CLL? 

Although several bispecific antibodies are FDA-approved for other types of non-Hodgkin lymphomas, they are still under review for CLL. Dr. Kittai stated the main reasons are that CLL dampens T-cell activity more than other cancers and tends to circulate widely in the blood, creating concerns about treatment efficacy and increased toxicity. 

Despite these challenges, the promise of bispecific antibodies in CLL remains high, with several clinical trials exploring combinations of bispecific antibodies with therapies such as venetoclax and lenalidomide to enhance T-cell efficacy and overall treatment outcomes. 

The FDA-approved bispecific antibodies for other types of non-Hodgkin lymphomas include epcoritamab (Epkinly), glofitamab (Columvi), and mosunetuzumab (Lunsumio). 

CLL patients who would like to receive treatment with a bispecific antibody can do so through the following clinical trials: 

• Epcoritamab for CLL clinical trial
• Glofitamab for CLL clinical trial 
• Mosunetuzumab for CLL clinical trial 

To learn more about CLL clinical trials, click here. If you have questions regarding signing up for a clinical trial, click the “Begin Now” button for HealthTree Patient Navigators to assist you. 

How Do Bispecific Antibody Brands Differ From One Another? 

The main differences between epcoritamab, glofitamab, and mosunetuzumab are how they are administered and for how long.  

• Glofitamab
  • Administered by intravenous infusion (IV). 
  • Fixed-duration therapy is given for a set period of up to 12 months and then stopped.  
  • Obinutuzumab is given first to help clear out cancer cells, reducing side effects.
• Mosunetuzumab
  • Administered by intravenous infusion (IV), but a version that is administered by subcutaneous injection is being developed. 
  • Fixed-duration therapy is administered for up to 17 months; however, patients can stop at eight months if they experience reduced signs and symptoms of their CLL. 
• Epcoritamab
  • Administered by subcutaneous injection (shot under the skin). 
  • Continuous-duration therapy meaning the medicine is given indefinitely until CLL cells stop responding to treatment. 

What are the Side Effects of Bispecific Antibodies?

Bispecific antibodies show a favorable safety profile compared to CAR T-cell therapies. The primary concern with bispecific antibodies is cytokine release syndrome (CRS), which occurs when the activated T-cells release a high level of inflammatory molecules called cytokines during the treatment process. 

CRS typically presents with symptoms like fever, which can escalate to more severe conditions such as low blood pressure and high heart rate. Despite its potential severity, CRS can often be managed at home with over-the-counter remedies like Tylenol and prescribed steroids as initial treatments. However, hospital admission is recommended for more severe or persistent symptoms.

Another notable side effect of bispecific antibodies is neurotoxicity, although it occurs less often than with CAR T-cell therapy, affecting fewer than 10% of patients. In more severe cases, this side effect may manifest as confusion or decreased responsiveness. 

Other risks include infections and prolonged low counts of various blood cells (cytopenias), which are generally less frequent but require careful monitoring. 

Encouragingly, recent studies and clinical trials indicate that even patients with significant comorbidities can tolerate bispecific antibodies well, with no deaths attributed to CRS reported in these studies. As such, while bispecific antibodies share some toxicities with other cancer therapies, their rapid availability and ease of administration over extended periods make them an important option in managing cancers.

In conclusion, Dr. Kittai's presentation reflects a cautious yet optimistic view toward bispecific antibodies in CLL treatment. As research progresses, these therapies may soon offer new hope for patients, especially those who have exhausted other treatment options. The ongoing trials and studies will be crucial in determining the efficacy and safety of bispecific antibodies for CLL, potentially leading to their approval and widespread use in the near future. 

Audience Q&A 

During the event, Dr. Kittai answered several patient questions. Some of these included: 

• How long, on average, do bispecific antibodies help limit the progression of CLL? (Timestamp 28:00) 
• Are there long-term side effects of bispecific antibodies? (Timestamp 30:00)
• How long do you have to wait to get vaccinated after bispecific antibody therapy? (Timestamp 34:47) 
• Is there any way to anticipate who might experience CRS? (Timestamp 36:34) 
• How long does it take for bispecific antibodies to start working? (Timestamp 45:50)

To listen to these questions’ answers, we invite you to watch the event recording by clicking here. 

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