Patient deaths halt clinical trial testing genetically engineered cells to treat cancer

Three patients have died in a clinical trial that is testing the use of genetically engineered immune cells known as CAR-T cells to treat acute lymphoblastic leukemia in adults. The Food and Drug Administration has temporarily halted the trial being conducted by the company Juno Therapeutics. According to the company, the deaths occurred after a chemotherapy drug, fludarabine was added to the treatment regimen.


Dr. Stephan Grupp, Novotny Professor of Pediatrics, University of Pennsylvania Perelman School of Medicine (webpage):

Expertise: Engineered T cell therapy; Dr. Grupp is running a similar trial funded by Novartis that use CAR T cells to treat pediatric acute lymphoblastic leukemia patients. 

“We have not seen significant brain swelling in any of our pediatric acute lymphoblastic leukemia patients on the Children’s Hospital of Philadelphia/Penn study treated with CTL019 CAR-T cells. Most of these patients received fludarabine, the same chemotherapy drug added to the patients in the trial being conducted by Juno Therapeutics. Central nervous system related side effects have been seen in these patients, including confusion, aphasia and seizures in a small number of patients, but these effects have all resolved.

“Obviously, it is always hard to attribute toxicity to the chemo as opposed to the CAR-T cells when both are given around the same time, but we believe the self-limited CNS side effects we have reported from our study are more likely to be due to the T cells.

“Right now, I don’t see this affecting other CAR-T trials or the field as a whole, since this issue appears not be seen more broadly. There may be some discussion about the appropriate role of the drug fludarabine, but this wouldn’t be a central issue.”


Dr. Mark Osborn, Assistant Professor, Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota (webpage):

Expertise: Gene therapy, genome editing, cellular therapy

“These events show the potential risks for CAR-T therapies utilizing vectors that mediate sustained expression that may be magnified in combinatorial chemotherapy regimens. Going forward, improved cellular therapies with optimized vector doses, expression patterns, and cooperative activity in the presence of chemo therapeutic agents will aid in mitigating side effects and achieving complete responses.”


Declared interests (see GENeS register of interests policy):

Dr. Stephan Grupp: Consults for Novartis.

No further interests declared.



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