Prevalence of adverse events following T-cell engaging bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR) T-cell therapy in patients with metastatic castrate-resistant prostate cancer (mCRPC): A meta-analysis.

128 Background: T-cell engaging bsAbs and CAR T-cell therapy have shown exceptional success in treating multiple hematologic malignancies. More recently, bsAbs have been FDA-approved to treat uveal melanoma and small cell lung cancer, demonstrating proof-of-concept for immune therapies beyond checkpoint inhibition to effectively treat solid tumors. bsAbs and CAR-T therapies are presently undergoing evaluation in trials for patients with mCRPC. Despite early successes with these classes of therapy, there are multiple ongoing challenges including dose-limiting toxicity, ‘on-target, off-tumor’ toxicity, and immune-effector cell related toxicity. This systematic review analyzes publicly available safety derived from ongoing clinical trials. Methods: An electronic systematic search through PubMed, CINHAL, Scopus, and Ovid was done to identify phase I/II clinical trials evaluating bsAbs or CAR-T therapy in patients with mCRPC reported prior to 9/30/2024. Treatment-related adverse events (TRAE) were collected, focusing on prevalence in bsAbs versus CAR-T. A random effects model was used for analysis. Results: Eleven trials with 511 patients evaluated bsAbs, and 5 trials with 55 patents studied CAR-T therapies. Mean patient age was 67 years [95% CI: 63, 71]. Cytokine release syndrome (CRS) occurred in 49% [24, 75] of patients; 53% [17, 86] on bsAbs compared to 43% [28, 59] on CAR-T. Only 4% [2, 7] of patients had CRS grade ≥3; 14% [2, 43] on CAR-T compared to 3% [2, 6] on bsAbs (p=0.05). Neurologic TRAEs occurred in 11% [3, 31] of patients; 39% [22, 60] on CAR-T compared to 5% [2, 13] on bsAbs (p= <0.01). Hematologic TRAEs occurred in 38% [14, 71] of patients; 34% [8, 75] on CAR-T compared to 43% [9, 86] on bsAbs. Hepatic TRAEs occurred in 31% [12, 59] of patients; 25% [12, 44] on CAR-T compared to 39% [9, 81] on bsAbs (p= 0.55). However, 8% of patients [3, 20] had grade ≥3 hepatic TRAEs, with 21% [5, 51] on CAR-T versus 5% [2, 10] on bsAbs (p=0.03). Musculoskeletal/dermatologic TRAEs were seen in 30% of patients [24, 37]; 30% [24, 38] on bsAbs and 29% [8, 58] on CAR-T (p=0.89). Renal TRAEs occurred in 15% [10, 23] of patients; 21% [5, 51] on CAR-T compared to 14% [8, 24] on bsAbs (p= 0.50). Gastrointestinal TRAEs were reported in 18% [10, 33] of patients; 14% [2, 42] on CAR-T compared to 19% [9, 36] on bsAbs (p= 0.69). Conclusions: In patients with mCRPC, bsAbs and CAR-T therapies produce similar hematological, musculoskeletal/dermatologic, renal and gastrointestinal TRAE rates. However, significantly higher rates of all-grade neurologic, grade ≥3 CRS and grade ≥3 hepatic TRAEs are reported with CAR-T therapy. These data highlight the need to appreciate the differences in toxicity profiles for these two classes of therapy and to practice appropriate vigilance during treatment.