PI-012 - CLINICAL EFFICACY OF CAR-T AND CAR-NK FOR THE TREATMENT OF HEMATOLOGIC AND SOLID TUMOR MALIGNANCIES: A SYSTEMATIC REVIEW AND META-ANALYSIS.

S. Chowdhury¹, G. Mugundu², J. Li²; ¹Takeda Development Center Americas Inc., Lexington, MA, USA, ²Takeda Development Center Americas, Inc., Lexington, MA, USA.

Background: Autologous chimeric antigen receptor (CAR)-T cell therapy has shown promising responses in patients with heme malignancies with 6 products approved by FDA. Efficacy data from allogeneic products such as CAR-T, CAR-Natural Killer (NK) -cell therapy is also emerging. The objective of this study was to systematically review and summarize the clinical efficacy of CAR-T and CAR-NK cell therapies for autologous and allogeneic therapies.

Methods: A comprehensive search was performed on PubMed, Beacon, and google to identify CAR-T and CAR-NK cell therapies with response data published as of August 2022. Data from both heme malignancies and solid tumors were included in the dataset. Random-effects model was used to analyze the best overall response rate (ORR) and complete response (CR) rate results in forest plots. Subgroup analysis was conducted per indication to assess the impact of CD28 or 4-1BB co-stimulatory domains. Funnel plots were generated to visually observe study bias.

Results: 68 studies with 3430 patients were included in the final dataset. In lymphoma, myeloma and leukemia, the ORR (CR rate) were 80% (70%), 92% (89%) and 79% (47%) for autologous products and 56% (48%), 56% (48%) and 70% (25%) for allogeneic products. Patients with liquid tumors had better responses than with solid tumors. Similar ORR and CR rates were observed for constructs with CD-28 or 4-1BB co-stimulatory domains with the latter having less heterogenicity across studies. 4 real-world observational studies were included and showed comparable responses with clinical trial data.

Conclusion: Overall, we found prominent responses with clinical trials and real-world observations regarding to autologous CAR-T treatment in heme malignancies. Response data on allogeneic products and in solid tumor is limited.