Abstract 2764: Safety and efficacy of CAR T and TCR therapies in solid tumors: A systematic review and meta-analysis, including a comparison with five phase II trials in hematologic malignancies used for the first FDA approvals of these agents

Abstract

Abstract Background: Adoptive cellular therapies (ACT) have met with significant success in hematologic malignancies. The number of ACT trials in solid tumors has been increasing, however data are limited on the overall safety and efficacy of ACT in this population. We aimed to conduct a systematic review and meta-analysis looking specifically at TCR and CAR-T in solid tumors and rates of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) relative to the current approved agents in hematologic malignancies. Methods: We conducted a systematic review of published studies/abstracts from January 2015 up to and including July 2021, selecting those that included ≥ 5 patients. Endpoints included rates and differences in CRS and ICANS. Response rates were evaluated. Statistical tests in the pooled data included χ2 and multivariable logistic regression. Results: This meta-analysis included a total of 1,250 patients [566 patients with solid tumors who had received ACT in phase I, II or I/II clinical trials; a comparison was made with five phase 2 clinical trials in hematologic malignancies used for the first FDA approvals of these agents (JULIET, ZUMA-1, ZUMA-2, TRANSCEND and KARMMA), encompassing 684 heme malignant patients]. Rates of CRS of any grade, CRS ≥ grade 3, ICANS of any grade, and ICANS ≥ grade 3 in solid tumors were 33.0%, 3.8%, 2.3% and 2.1%, respectively. Fever, hypotension, and hypoxia were experienced by 37.4%, 18.5%, and 8.5% of solid tumor patients, respectively. CRS, ICANS, fever and hypoxia in solid tumor patients did not differ by whether the ACT received was TCR or CAR T. Objective response (ORR = CR + PR) in patients with solid tumors was higher with TCR compared with CAR-T [odds ratio (OR) = 3.1, P=0.001] and with NY-ESO-1 than other targets (OR=2.0, P=0.031). Compared to hematologic patients treated with ACT, solid tumor patients treated with adoptive cellular therapies were significantly less likely to experience CRS of any grade (62.4% vs. 33.0%, P<0.001), CRS ≥ grade 3 (7.3% vs. 3.8%, P=0.043), fever (50.3% vs. 37.4%, P=0.001), hypoxia (34.1% vs. 8.5%, P<0.001) or hypotension (29.5% vs. 18.5%, P=0.006), ICANS of any grade (29.7% vs. 2.3%, P<0.001), or ICANS ≥ grade 3 (13.9% vs. 2.1%, P<0.001). However, objective response (20.1% vs. 75.4%, P<0.001) and clinical benefit (CBR = CR + PR + SD) (62.6% vs. 90.9%, P<0.001) rates for ACT were lower in patients with solid tumors than in patients with hematologic malignancies. Conclusions: CRS and ICANs were less prevalent in solid tumor cellular therapies. Based on this analysis, T-cell therapies in solid tumors are relatively safe, but further studies with larger populations and longer follow up are needed to address the role of these treatments in cancer. Citation Format: Mirella Nardo, Ji Y. Son, Goldy G. George, David S. Hong. Safety and efficacy of CAR T and TCR therapies in solid tumors: A systematic review and meta-analysis, including a comparison with five phase II trials in hematologic malignancies used for the first FDA approvals of these agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2764.