Dr Frank on the Initial Efficacy and Safety of CAR22 in Relapsed/Refractory LBCL

Matthew Frank, MD, PhD, assistant professor, medicine, Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, discusses preliminary results from a phase 1 trial (NCT04088890) of a CD22-directed CAR-T therapy (CAR22) in relapsed/refractory large B-cell lymphoma (LBCL).

The single-institution trial evaluated CD22-directed CAR-T therapy in patients with relapsed/refractory LBCL who progressed on prior CD19 CAR T-cell therapy. A total of 41 patients were enrolled, although 1 patient withdrew from the study. Of the remaining 40 patients, 38 had successful CAR22 manufacturing. The overall patient population was heavily pretreated, with median of 4 prior lines of therapy, Frank notes. Moreover, 79% of patients had elevated pre-LD lactate dehydrogenase, and one-third of patients had never previously experienced a complete response, Frank emphasizes.

Initial findings from the full dataset were reported at the 2023 EHA Congress. At a median follow-up of 18.4 months, CAR22 produced an overall response rate (ORR) of 68%, and 53% of patients achieved a complete response (CR) in the total population, Frank reports.

The agent produced less toxicities than most standard CAR T-cell therapies and was deemed safe, Frank continues. In the 29 patients who received CAR22 at dose level 1 of 1 x 10⁶ CAR+ cells/kg, all instances of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were grade 1/2. However, signals of CAR-hemophagocytic lymohistocytosis (HLH), which is characterized by high ferritin levels, cytopenias, coagulopathy, and liver abnormalities, he explains. Five patients experienced this adverse effect (AE), 2 of which received dose level 2 (3 x 10⁶ CAR+ cells/kg), Frank adds. However, all 5 patients experienced a CR.

Additionally, differences in survival outcomes between dose levels were numerically, but not statistically different, Frank says. The ORRs were 66% with dose level 1 and 78% with dose level 2. CR rates were also similar at 52% vs 56%, respectively.

The higher rate of CAR-HLH and higher-grade CRS associated with dose level 2, combined with comparable efficacy between dose levels, led to the selection of dose level 1 as the recommended phase 2 dose, Frank concludes.

Disclosures: Dr Frank reports participation on scientific advisory boards for Adaptive Biotechnologies, Kite-Gilead, and Cargo; and industry-contracted research for Allogene Therapeutics, Adaptive Biotechnologies, and Kite-Gilead.