17 September 2018

Following the announcement that the NHS has approved the use of CAR T-Cell therapy for children and young people with acute lymphoblastic leukaemia (ALL), BSH member Dr Maria Teresa Esposito offered her thoughts on what this news will mean for patients with the condition, and the long term prospects this treatment will offer. 

The NHS has announced that a revolutionary gene therapy treatment called chimeric antigen receptor T-cell (CAR-T) (Kymriah) will be offered to children and young adults under 25 years old with refractory acute lymphoblastic leukaemia (ALL).

Kymriah will be the first CAR-T childhood cancer treatment and the second gene therapy product available on the NHS, after the approval of Strimvelis a year ago.

Our immune system provides a strong defence against infectious diseases and cancer. However, pathogens and cancer cells develop several ways to escape the immune system. Kymriah is a custom made personalised drug that genetically reprograms the immune cells to recognise the cancer cells and kill them.

Developed by the University of Pennsylvania and Novartis, the treatment consists of a single shot of immune cells reprogrammed for killing the leukemic cells. Clinical trials have shown remarkable results.

The approval of Kymriah on the NHS follows the announcement of the NHS England’s CEO Simon Stevens in April this year to create three CAR-T centres in the UK in London, Manchester and Newcastle. This would be indispensable for the appropriate manufacturing and delivery of the drug and for the follow up of the patients.

Kymriah is a custom-made drug. Immune cells called T cells will be collected from the patients eligible for the drug using a procedure similar to blood collection. The cells will then be grown and genetically modified in a laboratory and then administered back to the patient with a procedure which resembles a transfusion.  

There is a lag period between collection of immune cells from the patient and development of engineered cells for administration. Patients might die while waiting for their engineered immune cells. Novartis has said that the turnaround times is around 22 days which might not be acceptable for all the patients.

Moreover, the side effects will need to be monitored closely. In clinical trials Kymriah has shown severe side effects that include the cytokine syndrome, which is an inflammation due to the massive activation of the immune system. The long-term effects are also unknown. We do not know yet if the patients that undertook Kymriah during the clinical trial and that are currently in remission can be considered cured or if they will eventually relapse, meaning that the leukaemia will come back.  We do not have any data to make any speculation on that. However, we must consider this drug as an extraordinary opportunity to prolong the survival of patients that at the moment do not have any other option.

Acute B-lymphoblastic leukaemia (ALL) accounts for 25% of all cancer in children under the age of 15. The standard treatment is based on chemotherapy followed by bone marrow transplantation. If the standard treatment fails or a bone marrow donor is not available or the patient relapses after bone marrow transplantation, there are no other therapeutic options and the chances of survival are slim.  It is estimated that 15% of cases do not respond to standard treatment. Kymriah represents therefore an opportunity for these children.

Dr Maria Tereas Esposito is Senior Lecturer in Biomedical Science at the University of Roehampton. You can read about her work in our Meet the Member piece from earlier this year.


 *The contents of this article do not reflect an official BSH position. We would value your thoughts on this article and hope it provokes discussion within the haematology community.