Dr Srour on Toxicities Associated With CAR T-Cell Therapy in RCC and Other Solid Tumors

Samer A. Srour, MB ChB, MS, assistant professor, Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses difficulties associated with the utility of the allogeneic CAR T-cell therapy CTX130 in patients with advanced clear cell renal cell carcinoma, as well as in other solid tumor patient populations.

CTX130 was evaluated in the phase 1 COBALT-RCC trial (NCT04438083), findings from which were presented at the 2024 AACR Annual Meeting. When considering commercially available CAR T-cell products for the management of hematologic malignancies, the foremost challenges associated with CAR T-cell therapy lie in its unique toxicities, Srour begins. These include cytokine release syndrome (CRS), neurotoxicity such as immune effector cell–associated neurotoxicity syndrome (ICANS), and the rare but serious complication known as hemophagocytic lymphohistiocytosis, (HLH), he explains. In the context of CAR T-cell therapy for solid tumors, particular attention is paid to these 3 distinctive toxicities, Srour adds.

The safety profile of CTX130 is promising, according to Srour. Notably, in COBALT-RCC, CRS events were limited to grades 1 and 2, aligning with observations from studies of similar CAR T-cell products, he expands. Encouragingly, no instances of ICANS or HLH were observed, marking a significant milestone in safety, Srour states. Moreover, infections, a concern associated with CAR T-cell therapies for hematologic malignancies, did not manifest as grade 3 or higher events attributable to CTX130, Srour notes. This comprehensive safety assessment underscores the favorable safety profile of CTX130 in the context of these high-risk patients, Srour reports.

The absence of severe CRS and ICANS, coupled with the lack of HLH occurrences, highlights the potential of CTX130 to mitigate the toxicities commonly associated with CAR T-cell therapy, he continues. The low incidence of grade 3 or higher infections further reinforces the favorable safety profile of CTX130 in this patient population, Srour says. These findings offer promising implications for the broader application of CTX130 in hematologic malignancies, indicating its potential to address critical safety concerns and deliver therapeutic benefits to patients, he concludes.