Gene therapy for cancer halted after patient death

Two trials assessing gene therapy for blood cancer have been put on hold by the US Food and Drug Administration (FDA), following a patient fatality.

The therapy, known as 'off-the-shelf' CAR-T immunotherapy, used genetically modified immune system T cells to target cancer, yet unlike other trials the cells were taken from a healthy donor instead of the patient. It was hoped this therapy would prove easier and less expensive to produce.

'Allogeneic production of CAR-T cells is cost-effective and results in remarkable off-the-shelf product, capable of being distributed worldwide', the manufacturer Cellectis had suggested in a video presentation.

The early-stage trials of the therapy, called UCART123, aimed to treat two types of blood cancer, blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute myeloid leukaemia (AML), in patients who did not respond to typical treatment or relapsed.

The 78-year old male patient who died was first to be treated in the BPDCN study. He experienced side effects in the form of lung infection and moderate cytokine release syndrome (CRS) at day five, severe CRS and blood vessel leakage on day eight, and death on day nine. CRS results from the excessive release of immune components called cytokines from targeted cancer cells and immune system cells.

The first patient in the AML study, a 58-year old female patient, received the same treatment at the same dose, and experienced similar side effects. Although intensive care treatment resolved the side effects, the AML study has also been put on hold until the development of appropriate safety measures.

Two days following the reported patient fatality, the FDA made a recommendation to lower the immunotherapy and supporting drug dosage.

'Cellectis is working closely with the investigators and the FDA in order to resume the trials with an amended protocol including a lowered dosing of UCART123,' the company said in a statement.

Cellectis's shares fell by 23 percent following the FDA’s notice. It is not the first to report patient death through CAR-T therapy trials. In March 2017, the pharmaceutical company Juno Therapeutics reported five patient deaths in response to personalised CAR-T therapy targeting acute myeloid leukaemia, a type of blood cancer. Similarly, Kite Pharma's trial on aggressive non-Hodgkin lymphoma has reported one patient death.

However last week, the FDA approved the first personalised CAR-T cell therapy for leukaemia (see BioNews 916).