Nearly half of the patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) who received AUTO1, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, had an ongoing complete remission (CR) three years after infusion.
Claire Roddie, MD, PhD, of the University College London Hospital National Health System Foundation Trust, and colleagues conducted the research and presented their findings during the 2022 American Society of Hematology Annual Meeting.
The researchers generated AUTO1, which is a “fast off-rate CD19 binding domain CAR designed to reduce immune toxicity and improve engraftment,” by using a closed process from nonmobilized patient-leukapheresis products.
The study enrolled 26 patients with B-cell ALL, 25 of whom underwent leukapheresis. Of those 25 patients, 20 received an infusion of AUTO1.
Patients who were at least 16 years old received conditioning with three doses of fludarabine 30mg/m2 three times and one dose of cyclophosphamide 60 mg/kg. Patients with ≥20% bone marrow blasts at day zero received an AUTO1 dose of 10×106, while those with <20% bone marrow blasts at day zero received a dose of 100×106. At day nine, patients received a second dose of AUTO1 if they did not develop grade 3 to 5 cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. The researchers administered the second dose so each patient would receive a total dose of 10×106.
Of the 20 patients who received AUTO1 infusions, eight (40%) had an ongoing CR at a median follow-up of 36 months after infusion. In the patients who had an ongoing CR, seven of eight (88%) maintained their remission without any further therapy, including tyrosine kinase inhibitors. Long-term remission was associated with CAR-T persistence in seven of the eight (88%) patients at the last follow-up.
“AUTO1 has a tolerable safety profile in patients with [relapsed or refractory] B-cell cancers despite high disease burden,” Dr. Roddie and colleagues concluded. “In the [B-cell] ALL cohort, long-term follow-up indicates that 40% of patients continue in remission post-AUTO1.”
Roddie C, Dias Alves Pinto J, O’Reilly MA, et al. Safety, efficiency and long-term follow-up of AUTO1, a fast-off rate CD19 CAR in relapsed/refractory B-cell acute lymphoblastic leukaemia and other B-cell malignancies. Abstract #3318. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.