Combining anti-CD19 CAR T-cell therapy with ibrutinib for treating chronic lymphocytic leukemia

The study aimed to investigate if anti-CD19 chimeric antigen receptor (CAR) T-cell therapy and ibrutinib (Imbruvica) could be combined for the treatment of patients with chronic lymphocytic leukemia (CLL).  

This study concluded that adding anti-CD19 CAR T-cell therapy (CART-19) to ibrutinib treatment in these patients led to durable remissions.  

CAR T-cell therapy is a type of immunotherapy approved in the US for treating certain types of blood cancers. It involves changing T cells (a type of immune cell) in the lab so they would attack and kill cancer cells. In patients with CLL who achieve complete remission (CR) with CAR T-cells, remissions are very durable.   

Ibrutinib is a type of targeted therapy called a tyrosine kinase inhibitor (TKI). It blocks a protein on CLL cells that stops the growth and spread of CLL. Data from experimental studies suggested that CART-19 and ibrutinib may be more effective when combined in patients with CLL. Therefore, it is important to evaluate whether adding CART-19 to ibrutinib treatment would be safe and effective in patients with CLL.  

This study involved 19 patients with CLL on ibrutinib treatment. Patients were not in CR despite at least 6 months of ibrutinib therapy. All patients received autologous antiCD19 humanized binding domain T cells (huCART-19). The average follow-up time was 42 months.  

18 patients developed cytokine release syndrome (CRS) and 5 patients developed neurotoxicity. CRS is a collection of symptoms that can develop as a side effect of immunotherapy. It involves a large number of immune cells released into the blood. Symptoms include fever, headache, or nausea. Neurotoxicity involves a disruption in the regular activity of the nervous system.  

At 12 months, 72% of patients had no measurable residual disease (MRD). 

The estimated overall survival (OS) rate at 48 months was 84%. The estimated survival rate without cancer worsening at 48 months was 70%.  

Of 15 patients with undetectable MRD at 3 or 6 months, 13 remained in ongoing CR at the last follow-up. 

This study concluded that in patients with CLL not achieving a CR despite at least 6 months of ibrutinib, adding huCART-19 led to a high rate of deep and durable remissions. 

This study had a small number of participants. This study was funded by Novartis, the manufacturer of CART-19.