T-cell redirecting therapies, including T-cell engagers (TCEs) and CAR-T, are under investigation in metastatic castration-resistant prostate cancer (mCRPC). Despite their promising therapeutic potential, these therapies remain in early stages of development due to treatment-related adverse events (TRAEs). This study aims to quantify the frequency and severity of adverse events in clinical trials with a pooled analysis.
A systematic search of PubMed, CINHAL, Scopus, and Ovid was conducted to identify clinical trials evaluating TCEs or CAR-T in patients with mCRPC. Types and frequencies of TRAEs were collected and analyzed using a random-effects model.
Thirteen TCEs trials involving 861 patients and five CAR-T trials involving 55 patients were identified. Cytokine release syndrome occurred in 59% (95% Confidence interval: 25, 86) and 43% (28, 59) with TCEs and CAR-T, respectively. Neurologic TRAEs occurred in 39% (22, 60) with CAR-T compared to 9% (4, 17) with TCEs (p < 0.0001). Hematologic and hepatic TRAEs occurred in 34% (8, 75) and 25% (12, 44) with CAR-T, compared to 23% (7, 56) and 33% (12, 64) with TCEs, respectively. Musculoskeletal/dermatologic TRAEs occurred in 33% (24, 42) and 29% (8, 58) with TCEs and CAR-T, respectively. Renal and gastrointestinal TRAEs occurred in 21% (5, 51) and 14% (2, 43) with CAR-T, compared to 15% (8, 25) and 21% (12, 36) with TCEs, respectively.
These data underscore the TRAE profiles associated with these therapies and emphasize the importance of differentiating off-target toxicities from immune effector cell-toxicities to inform the development of effective TRAE mitigation strategies.
The oncologist. 2026 May 02 [Epub ahead of print]
Abhiraj Saxena, Marc Yorker, Nicholas A Zorko, Vivek Narayan, Bilal A Siddiqui, Biren Saraiya, William J Tester, Patrick J Mille, Amy L Shaver, Nikita Nikita, Grace L Lu-Yao, Wm Kevin Kelly, Kevin K Zarrabi
Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA., Department of Medicine, Masonic Cancer Center, University of Minnesota-Twin Cities, Minneapolis, MN, USA., Department of Medical Oncology, Abramson Cancer Center and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Division of Medical Oncology, Rutgers Robert Wood Johnson Medical School.