A patient involved in a late-stage program by Kite Pharma for the CAR-T drug KTE-C19 has died from cerebral edema, the same brain swelling condition that killed five patients in Juno Therapeutics' clinical trial last year.

Both companies have been developing the same type of cutting-edge cancer immunotherapy called CAR-T. Kite's report has informed the FDA that there was no pause or halt to the study.

The death occurred in late April and has raised caution about the immunotherapy drugs that have promised high hopes even as their side effects have become apparent. Kite previously managed to get ahead of Juno Therapeutics without a death due to cerebral edema after treating hundreds of patients.

"It took about two days of progressively worsening neurological events," said KITE CMO Dr David Chang. "In this time the patient's overall condition was deteriorating."

Kite's drug similar to Juno's, raising concerns

The patient who was evaluated for safety in a late-stage trial for the drug, suffered from refractory non-Hodgkin lymphoma which was "explosive" and "rapid progressing and had a lot of symptoms from the tumour," said Dr Chang. The patient also had fever - but tests for underlying infections came back negative - and continued to develop multiple organ failure along with brain swelling and succumbed in late April.

But many investors and sceptics have harped on the fact that although patient numbers are too small to draw firm conclusions, KTE-C19 only differed from JCAR015 in their binding region. The precise cause of the cerebral edema with CAR-T is also not understood.

However, a spokesperson for Kite noted that "we don't see any safety concerns" and development studies will continue as planned. Kite also reminded that the overall incidence of KTE-C19 related grade 5 events stands at 2% in approximately 200 patients - 300 of its patients treated in NCI studies were included - that were treated in the study, supporting the benefits of the immunotherapy.

This might set back Kite's plans to review the treatment and seek approval with the FDA by the end of this year. Kite Pharma, along with competitor Novartis were seen as leading players in the therapy after Juno was forced to pull the plug on their program which resulted in five deaths.

Safety expansions to be explored for CAR-T therapies

To develop a CAR-T therapy, a patient's own immune cells are harvested and re-engineered to attack their cancer. Early results have been shown to be promising but many scientists caution that they are only just beginning to understand the field. Some patients suffered cytokine storms that occasionally turned lethal. No CAR-T therapies have been approved yet.

Doctors of all clinical trials have emphasised that the patients who have died during testing of experimental therapies are already very sick and have exhausted all traditional therapy options. Referring to the patient who died last month, Kite said that "those involved in the care felt that CAR-T therapy was the only remaining option."

Now companies are testing new ways to avoid the toxic side effects. Dr Chang said they would continue to consider the efficacy and safety of the drug as more studies proceed, such as the addition of an anticonvulsant and an immunosuppressive drug. MIMS

Read more:
Why one CAR-T therapy worked and another failed
Clinical trial halts as two patients die from cerebral edema, FDA to answer questions
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