CTC study CARPALL presented at 2022 EHA conference
20 July 2022
A CTC study of treatment for children and young adults with blood cancer was presented at a European Haematology Association conference in Vienna last month. 

The CARPALL study has involved young patients with leukaemia which has either returned after treatment, or is likely to return. The therapy on the trial involves collecting a patient’s T-cells (a type of white blood cell in the body’s immune system) and altering them in order that they can specifically target and fight cancer cells in the blood.

The CTC’s CARPALL team has provided the following summary of the presentation: 

Dr Sara Ghorashian presented the CARPALL study at the 2nd European Haematology Association (EHA) congress on 11th June 2022. 

CARPALL is a phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in children and young adults with high risk, relapsed CD19+ and/or CD22+ Acute Lymphoblastic Leukaemia (ALL). 

We have previously published results1 from the study where patients were treated with CD19 CAR T-cells. These are patients’ own T-cells genetically modified to recognise the CD19 protein present on the leukaemia cells and attack them. The results were encouraging, with 12 out of 14 treated patients achieving a complete response. The safety profile was also good, with no severe Cytokine Release Syndrome (CRS) observed. 

However, there were 6 relapses. 5 of these patients ‘lost’ the CD19 protein on their leukaemia cells and their cancer came back as the CD10 CAR T-cells no longer could recognise the leukaemia cells (this is called ‘antigen negative relapse’). In an attempt to prevent this, we further modified the CAR T-cells to also recognise another protein, CD22 (present on the leukaemia cells) in addition to the CD19 target and attack them. We then treated further 11 patients with these CD19/22 CAR T-cells.

Dr Ghorashian presented the new data from these 11 patients who received treatment with CD19/22 CAR T-cells. She remarked: 'This was an opportunity to present exciting findings from a ground-breaking study. Dual targeting studies to date have not shown an improvement in ALL outcomes compared to single antigen targeting. This is partly because the technical challenges of delivering effective dual targeting CAR T products is considerable! Our early results are encouraging, but will need longer follow-up'.
 
The main takeaways from the presentation were as follows:

• The safety profile of the new CD19/22 CAR T-cells is favourable, again there has been no severe Cytokine Release Syndrome (CRS), but there was an atypical grade 4 ICANS event 
• Excellent CAR T expansion
• 9 out of 11 patients achieved complete response and 2 patients did not respond to treatment 
• 2 out of 3 pts who did not have the CD19 protein on their leukaemia cells achieved complete response demonstrating the efficacy of the CD19/22 CAR T-cells in targeting the CD22 protein on the leukaemia cells
• There has been no antigen negative relapse seen in responding patients

The results are exciting and the CARPALL team look forward to analysing the data once all patients have been treated. 

More details on the CARPALL study can be found here

Ghorashian, S., Kramer, A.M., Onuoha, S. et al. Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nat Med 25, 1408–1414 (2019). 
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