How does CAR T-cell therapy affect an enhanced anti-leukemia effect? Could higher doses influence toxicity or change patient outcomes? According to an article in the Pharmacy Times, researchers sought to find answers to these questions regarding tisagenlecleucel for young patients (under 26) with B-cell acute lymphoblastic leukemia (B-cell ALL or B-ALL). 

The National Cancer Institute (NCI) explains that tisagenlecleucel is a CAR T-cell therapy:

made using a patient’s T cells [and] a gene for a special receptor called chimeric antigen receptor [that] is added to the T cells in the laboratory. Tisagenlecleucel binds to a protein called CD19, which is found on some leukemia and lymphoma cells.

Tisagenlecleucel has been used to treat patients with B-ALL for whom other treatments have not worked. Currently, an estimated ⅕ of patients don’t respond well to other therapies. 

However, doctors still struggle with determining the best dosing for tisagenlecleucel. So researchers recently sought to understand the correct dose to inform dosing and improve patient outcomes moving forward. Altogether, 185 patients enrolled within this study. Over a 1-year period, participants received a range of tisagenlecleucel doses (all within the FDA-approved range). 

Of those receiving a lower tisagenlecleucel dose (0-1.3 million cells/kg), 59% survived for a year, compared to 86% receiving the higher dose (2.4-5.1 million cells/kg). As a result, researchers determined that tisagenlecleucel improved overall survival by 30%. Additionally, the therapy was found to remain safe and well-tolerated even in higher doses. 

What is Acute Lymphoblastic Leukemia (ALL)?

Acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow. You may also hear it referred to as acute lymphocytic leukemia. ALL often progresses rapidly. It results from errors in the DNA of bone marrow cells. This causes the production of abnormal and immature blood cells, which then progress into cancerous lymphoblasts. Risk factors include having a genetic disorder, having a sibling with ALL, radiation exposure, and prior cancer treatment. Symptoms can (but do not always) include:

• Shortness of breath
• Pallor (abnormally pale skin)
• Bone pain
• Frequent infections
• Fatigue and general weakness
• Swollen lymph nodes
• Bleeding from the gums
• Frequent nosebleeds
• Anemia (low red blood cell count)
• Neutropenia (low white blood cell count)
• Thrombocytopenia (low platelet count)