Exploring the Effectiveness of CD19 and CD22 CAR-T Cell Therapies in ALL

Chimeric antigen receptor (CAR-T cell therapy) has been shown to improve outcomes in people with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).  Much of the research in this area has come from early-stage clinical trials with limited patient enrollment.  A recent study combined data from multiple trials to study the effectiveness and safety of CAR-T therapy among individuals with ALL.

What Is CAR T-cell Therapy for ALL?

CAR-T cell therapy uses genetically modified T-cells to recognize and target cancer cells. T-cells are white blood cells that help the body's immune system identify and respond to disease. CAR-T cell therapy is used to treat a variety of cancers. It can be effective when other treatments are not feasible or no longer working.

There are currently three FDA-approved CAR-T cell treatments available for the treatment of relapsed or refractory ALL: KYMRIAH, TECARTUS, and AUCATYZL.  

In a recent study, researchers identified 30 trials involving 1,154 patients with ALL to include in the analysis. Among these, 22 trials studied CAR T-cell therapies targeting surface protein CD19 on cancer cells, five focused on CD22, and three targeted both CD19 and CD22. 

The most commonly used co-stimulatory domain (a molecule that strengthens cell activation and helps ensure a more sustained immune response) was 4-1BB (67%), followed by CD28 (20%). Most trials (60%) enrolled both children and adults, and about one-third of participants (32%) had previously received an allogeneic stem cell transplant.

Significant Clinical Responses and MRD Negativity

Among 30 eligible trials involving 1,154 patients with relapsed or refractory acute lymphoblastic leukemia (R/R ALL):

• The overall response rate (ORR), or percentage of people with a partial or complete response to treatment, was 81%.
• 73% of patients had no detectable cancer cells remaining after treatment, based on very sensitive tests. This is called a minimal residual disease-negative (MRD-negative) response.  

You can read more about MRD-negativity in ALL here.

ALL patients treated with CD19-CAR or CD19/22-CAR products had higher MRD-negative response rates than those treated with CD22-CAR.

Which treatment features made a difference?

People who had never received CAR T-cell therapy before had higher MRD-negative rates (75%) than those who had already tried it (61%).  MRD rates were better in clinical trials that included children only compared to trials that included adults only or both adults and children. Additionally, therapies using 4-1BB as a costimulatory domain had better results than those using CD28. 

Targeting different proteins affected safety and effectiveness

Most studies targeted CD19, with some using CD22 or a combination. Therapies that targeted CD19 or both CD19/CD22 had better MRD-negative results than those targeting CD22 alone.  However, CD22-targeted therapies had fewer side effects.

What were the survival results?

In 15 studies that reported survival, Overall survival ranged from 7.2 to 23.7 months, and median overall survival was 14.6 months.  Relapse-free survival ranged from 2.53 to 15.2 months. What were the side effects?

85% of study participants experienced cytokine release syndrome (CRS), a common reaction that occurs when the immune system is highly active. CRS can cause fever, nausea, fatigue, and breathing problems.

ICANS (immune-related neurotoxicity) was more common in people who received CD19-targeted therapy. This condition affects the brain and nervous system and may cause confusion, seizures, or other issues.

Conclusion

CAR T-cell therapy can offer strong response rates in people with relapsed or refractory ALL. This pooled analysis shows that some types of CAR-T therapies, like those using the 4-1BB domain, may be more effective and have fewer side effects. Understanding which treatment characteristics lead to better outcomes can help patients and their care teams make more informed choices.

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Source: 

• Ash 2024 Clinical Outcomes in patients with R/R ALL receiving CAR-T