The immune system usually helps your body fight off infections and detects and destroys abnormal cells. Antibodies are Y-shaped proteins that generally help the body recognize pathogens such as viruses and bacteria. They bind to unique molecules on the outside of cells known as antigens (i.e., CD20 is an antigen expressed on the surface of B cells).
Monoclonal antibodies (i.e., rituximab) are already widely used in the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL). These lab-created antibodies are designed to mark cancer cells by binding to specific targets such as CD20, and they help the immune system better recognize and destroy cancer cells.
At the annual meeting of the American Society of Hematology (ASH) 2020, our own Brian Koffman interviewed Dr. Benjamin Heyman, a hematologist at UC San Diego Health in San Diego, CA. They discussed the monoclonal antibody cirmtuzumab, which targets a novel antigen, ROR1.
- Cirmtuzumab is a monoclonal antibody that targets a stem cell antigen called ROR1.
- ROR1 is a protein expressed in several cancers, including CLL/SLL, but it is not found in normal healthy cells.
- Patients whose cancer expresses stem cell markers such as ROR1 tend to have more aggressive disease, a higher risk of metastasis, and a poorer prognosis.
- Cirmtuzumab has been studied in early-stage clinical trials as a single agent and in combination with ibrutinib, and it has been shown to be very safe thus far.
- Approximately 1 in 3 patients treated with venetoclax, with or without anti-CD20 monoclonal antibodies such as rituximab, cannot achieve undetectable measurable residual disease (uMRD).
- Patients who stop venetoclax therapy without achieving uMRD are at higher risk of relapse, and their cancer cells have gene-expression signatures reflective of high levels of ROR1 signaling.
- Heyman and his colleagues will be conducting a phase 2 clinical trial to test whether adding cirmtuzumab to the treatment regimen of patients who were unable to achieve uRMD with venetoclax will help them get to remission with uRMD.
- Patients will receive cirmtuzumab + venetoclax for at least six months.
- If you are interested in participating in this study, more information can be found here.
Venetoclax is a very potent and effective treatment for CLL/SLL, but it is not enough for some patients to get them into deep remission with uMRD. Studies of patient samples suggest that specific stem cell markers such as ROR1 contribute to the underlying biology that makes these particular cancer cells more resistant to treatment with venetoclax. Cirmtuzumab is a novel monoclonal antibody that targets ROR1, and researchers hope that it will help get patients with harder to treat CLL/SLL into remission.
Please enjoy this interview with Dr. Heyman from the virtual ASH meeting held in December 2020.
You can read the actual ASH abstract here: Cirmtuzumab Consolidation for Treatment of Patients with Detectable CLL on Venetoclax
Take care of yourself first.
Ann Liu, PhD