Association between bispecific T cell engager (BiTE) therapy and inflammatory adverse effects (AEs) in patients with metastatic castration-resistant prostate cancer (mCRPC).

e14534 Background: Cancer immunotherapies have offered limited efficacy in treating mCRPC. A novel class of immunotherapy are BiTEs, which target both a specific cancer antigen and CD3 to enhance T cell anti-tumor activity. Although BiTEs are a promising avenue for cancer research, their safety profiles are not well-understood. Thus far, it is known that first-in-class blinatumomab is associated with AEs such as cytokine release syndrome, neurotoxicity, and febrile neutropenia. Given their mechanism of action and possible propensity to produce a general inflammatory environment, we aimed to explore the systemic and inflammatory AEs of BiTEs in mCRPC patients. Methods: A retrospective chart review was performed on an IRB-approved database. Inclusion criteria included a history of mCRPC and BiTE therapy. There were no exclusion criteria. Study objectives were to evaluate whether BiTE therapy led to de novo inflammatory AEs or exacerbation of pre-existing inflammatory disorders. AEs were defined/graded as immune system disorders per Common Terminology Criteria for Adverse Effects v5.0. Results: 24 mCRPC patients in our clinic received at least 1 dose of BiTE therapy. Mean (range) age was 67.3 (54-79) years. 5 (20.8%) had pre-existing inflammatory disorders. Mean (range) treatment course was 14 (0-44) weeks. 6 (25.0%) discontinued due to inflammatory AEs, 15 (62.5%) discontinued due to disease progression, 1 (4.2%) discontinued due to noncompliance, and 2 (8.4%) are currently on BiTE therapy. Notable de novo AEs included arthralgia (8.4%), thrombophlebitis (8.4%), myocarditis (4.2%), giant cell arteritis (4.2%), and pneumonitis (4.2%). Patients with pre-existing inflammatory conditions (5/5) were statistically more likely to develop inflammatory AEs after BiTE therapy initiation compared to those without (4/19) (p < 0.01). Of the 9 patients who developed inflammatory AEs, 6 (66.7%) developed inflammatory AEs after the first dose of BiTE therapy. After the first dose, mean C-reactive protein was significantly elevated in patients with pre-existing inflammatory conditions (10.0) compared to those without (1.6) (p = 0.041). Conclusions: Our analysis suggests that BiTE therapies are associated with inflammatory AEs other than cytokine release syndrome, neurotoxicity, and febrile neutropenia. In particular, some of our patients developed vasculitis, myocarditis, or pneumonitis. Furthermore, patients with pre-existing inflammatory conditions are at significantly greater risk of developing inflammatory AEs compared to patients without pre-existing inflammatory conditions. Thus, patients with pre-existing inflammatory conditions who are receiving BiTE therapy should be cautiously observed. Additional data from larger BiTE therapy clinical trials is needed to further support these findings.