A modified type of CAR-T cell therapy may spare blood cancer patients from the need for toxic chemotherapy that is usually given in advance, an early-stage trial suggests.
CAR-T cell therapy involves immune cells called T cells. They are harvested from the patient’s blood, modified to produce a protein that targets the cancer and multiplied until there are millions of them, and then reinfused into the patient. Toxic chemotherapy drugs are typically given in advance, to suppress the immune system and boost the effect of the CAR-T cells.
The modified version tested in a Phase 1 trial used a specific type of T cell known as T memory stem cells that can renew themselves, last for years, and differentiate into many other T cell subsets.
For the study, one group of patients with a variety of blood cancers who had already been unsuccessfully treated with bone marrow transplants were re-infused with the T memory stem cells. The others received standard CAR-T cell infusions, a therapy itself only about a decade old. No one received chemotherapy beforehand.
Complete response rates in which the cancer became undetectable were 45% in the T stem cell group compared with 10% in the standard cohort. Overall response rates were statistically similar in the two groups, the researchers reported in Cell.
“Seeing patients achieve complete responses at (low) doses... without chemotherapy preconditioning, validates years of preclinical work and opens a new chapter in CAR-T cell design,” study leader Luca Gattinoni of the Leibniz Institute for Immunotherapy in Regensburg, Germany said in a statement.
The CAR-modified T memory stem cells multiplied faster and functioned longer than standard CAR-T cells, even though the standard cohort received a median of 290 million modified cells versus 66 million in the memory stem cell group.
The median time to adverse events or disease progression was also similar, at 3.3 months in the standard CAR-T cell cohort and 4.9 months in the CAR-T stem cell cohort. Four T stem cell recipients went more than two years without disease progression.
Patients in the memory stem cell group also had lower rates of a common and potentially serious inflammatory reaction triggered when CAR-T cells become overactive in the body, the researchers said.
