BiTEs vs. ICIs in lymphoma, leukemia, and myeloma: Which immunotherapy reigns supreme? A systematic review and meta-analysis.

Abstract

e14524 Background: Hematologic malignancies, including leukemia, lymphoma, and myeloma, pose significant challenges due to their complex biology. Advances in immunotherapies, such as bispecific T-cell engagers (BiTEs) and immune checkpoint inhibitors (ICIs), have transformed treatment. While both harness the immune system, they differ in mechanisms and targets. A comparative assessment of their efficacy and safety is crucial for optimizing care. BiTE monotherapy has shown superior efficacy over ICIs, particularly in targeting CD19 in NHL and BCMA in multiple myeloma. However, this benefit comes with a higher risk of grade 3 neutropenia, prompting exploration of combination therapies for synergistic effects. Clinicians must weigh BiTEs' efficacy against neutropenia risks, potentially requiring GCSF support. BiTEs' success is driven by their targeted approach and the "bystander effect," underscoring the need to understand their mechanisms and risks. Methods: We conducted a literature search across PubMed, Web of Science, Cochrane Library, and Google Scholar (1990–2025), including clinical trials on BiTEs or ICIs as monotherapies. Primary outcomes were objective response rate (ORR) and grade 3+ adverse events (AEs). Results: Analysis of 31 trials (2,507 patients) revealed BiTEs achieved higher ORRs than ICIs in NHL (34.1% vs. 21.9%), multiple myeloma (60% vs. 4.2%), and ALL (47.1%). Common grade 3+ AEs with BiTEs included neutropenia (45.2%) and cytokine release syndrome (12.9%), while ICIs were associated with anemia (14.4%). Conclusions: BiTEs are more effective than ICIs in NHL and multiple myeloma, likely due to targeting CD19 and BCMA. However, their higher AE risk necessitates further research to optimize use and minimize adverse effects.