“Off-the-Shelf" CAR T-Cell Therapy for CLL

CAR T-cells made from a CLL patient’s own T-cells (autologous) are often linked to T-cell exhaustion, causing treatment to not work well for most patients. Creating CAR T-cells from healthy donors’ T-cells (allogeneic) may overcome the obstacle of T-cell exhaustion. Learn about cema-cel, an allogeneic CAR T-cell therapy for CLL patients; and the ongoing ALPHA2 study, which is still recruiting participants. 

Is Autologous CAR T-Cell Therapy Effective for CLL? 

CLL patients who are intolerant to BCL-2 inhibitors like venetoclax (Venclexta, AbbVie) and BTK inhibitors need more treatment options. In this situation, people may turn to the new FDA-approved CAR T-cell therapy liso-cel (Breyanzi, BMS). Liso-cel enhances a patient’s own T-cells to kill CLL more effectively. T-cells that come from the patient are referred to as autologous (self). 

Unfortunately, one of the problems with liso-cel for CLL is that the treatment only helps 20% of patients achieve a complete reduction of disease signs and symptoms. Some patients experience T-cell exhaustion, causing the therapy not to work well. 

What is Allogeneic CAR T-Cell Therapy? 

With the hope of mitigating the issue of T-cell exhaustion, scientists created an allogeneic CAR T-cell therapy. Allogeneic means the T-cells come from healthy donors. These donor T-cells may not become exhausted to the same extent as cancer patients’ T-cells. This concept is still being evaluated through research. 

Another key advantage of allo-CAR T-cell therapy like cema-cel (ALLO-501A, Allogene Therapeutics) is that they are prepared in advance, so CLL patients don’t need to wait multiple weeks for treatment to be created from their own T-cells. These ready-to-go medicines are often called “off-the-shelf” therapies, and they are game changers for patients who urgently need to start treatment. 

To support a patient’s body in accepting donor CAR T-cells, cema-cel has specific genetic edits that reduce the risk of rejection, and patients are pre-treated with an anti-CD52 monoclonal antibody called ALLO-647. 

Where Can I Receive Cema-Cel Therapy? 

The ALPHA2 study is administering cema-cel to CLL patients whose cancer stopped responding to or returned after prior therapies (relapsed/refractory). The decision to add CLL patients to the ALPHA2 study came after seeing large B-cell lymphoma patients benefit from cema-cel treatment: 53.3% of patients experienced a complete reduction of cancer signs and symptoms. It is hoped that CLL patients will achieve similar results. 

Click here to check your eligibility for receiving cema-cel. 

New medicines like cema-cel are a hopeful step in the direction of improving treatment options for the relapsed/refractory CLL patient community. HealthTree looks forward to future data from the ALPHA2 study which may reveal whether allo-CAR T-cell therapy can reduce T-cell exhaustion and improve patient outcomes. 

For more general information about how CLL clinical trials work, click here. 

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Sources: 

• Allogene Therapeutics Announces 2024 Platform Vision to Redefine the Future of CAR T Led by ALPHA3, the Industry's First Pivotal Trial for Frontline Consolidation in Large B-Cell Lymphoma
• Clinical Update: TALEN-Edited CAR T-Cell Therapy for Large B-Cell Lymphoma
• Safety and Efficacy of ALLO-501A Anti-CD19 Allogeneic CAR T Cells in Adults With Relapsed/​Refractory Large B Cell Lymphoma, Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (ALPHA2) (ALPHA2)
• The immunological function of CD52 and its targeting in organ transplantation
• Phase 1 results with anti-CD19 allogeneic CAR T ALLO-501/501A in relapsed/refractory large B-cell lymphoma (r/r LBCL).