Clinical bottom line
Bispecific T-cell engager (BiTE) therapies represent a novel immunotherapeutic approach for hematologic malignancies, harnessing T-cell cytotoxicity to target tumor cells. However, patients receiving BiTE therapy are at increased risk for infectious complications, including protracted viral infections and immune-mediated adverse effects that may complicate infection management. Current evidence highlights the need for vigilant infection monitoring, tailored antimicrobial prophylaxis, and multidisciplinary care to balance infection risk with therapeutic efficacy. While data remain limited, emerging reports underscore the importance of early recognition and management of infectious and inflammatory complications in this population.
What the evidence shows
BiTE therapies, such as those targeting B-cell maturation antigen (BCMA) in multiple myeloma, have demonstrated promising anti-tumor activity by redirecting cytotoxic T cells to malignant cells (Tian et al., 2021). However, the immunomodulatory mechanism also predisposes patients to infectious risks. Palmen et al. (2023) reported protracted viral infections, particularly reactivations of herpesviruses, in multiple myeloma patients receiving BCMA-targeted BiTE therapy, suggesting impaired viral clearance possibly related to T-cell exhaustion or depletion. These infections were often prolonged and required extended antiviral therapy.
Beyond infectious risks, BiTE therapy can induce inflammatory adverse effects, including cytokine release syndrome and immune-mediated neuropathies, which may mimic or exacerbate infectious presentations (Girgis et al., 2025; Xu et al., 2023). Such immune-related toxicities complicate clinical assessment and may necessitate immunosuppressive interventions that further increase infection susceptibility. Marar et al. (2023) also highlighted cardiotoxicities associated with BiTE therapy, which may indirectly impact infection risk through organ dysfunction.
Protocols accompanying BiTE administration emphasize close monitoring for infections and immune-related events, with recommendations for prophylactic antimicrobials tailored to patient risk factors and local epidemiology (protocols.io, 2017). However, standardized guidelines remain lacking, and management often relies on extrapolation from other immunotherapy contexts such as CAR T-cell therapy or hematopoietic stem cell transplantation (Kahraman et al., 2021).
Caveats and uncertainty
The evidence base for infection management in patients receiving BiTE therapy is limited by small cohort sizes, heterogeneous malignancies, and evolving therapeutic regimens. Most data derive from observational studies or case series rather than randomized trials, limiting causal inference. The relative contribution of underlying disease, prior therapies, and BiTE-specific immune modulation to infection risk is not fully delineated.
Additionally, the spectrum of infectious pathogens and optimal prophylactic strategies remain incompletely characterized. Viral infections appear prominent, but bacterial and fungal infections are also reported, particularly in heavily pretreated patients. The impact of emerging BiTE constructs with varying targets and affinities on infection risk is unknown.
Furthermore, immune-mediated toxicities may confound infection diagnosis and management, and the balance between immunosuppression for toxicity control and infection risk requires careful clinical judgment.
How this may change practice
Clinicians managing patients with hematologic malignancies undergoing BiTE therapy should maintain a high index of suspicion for infections, particularly viral reactivations, and implement proactive surveillance strategies. Baseline screening for latent infections and consideration of antiviral prophylaxis may be warranted, especially in multiple myeloma patients receiving BCMA-targeted BiTEs.
Multidisciplinary collaboration involving infectious disease specialists, hematologists, and immunologists is essential to optimize infection prevention and treatment while managing immune-related adverse events. Early recognition and differentiation of inflammatory toxicities from infections can guide appropriate use of immunosuppressants and antimicrobials.
As evidence evolves, incorporation of infection risk stratification into BiTE treatment protocols and development of consensus guidelines will be critical. Clinicians should also counsel patients regarding infection signs and ensure timely access to diagnostic and therapeutic resources.