Bispecific Antibodies & CAR-T Therapy: Infection Risk Disparities Demand Proactive Pharmacy Strategies
Nearly one-third of patients undergoing treatment with bispecific antibodies for multiple myeloma face infection and immune dysregulation, a rate significantly higher than those receiving CAR-T cell therapy. This stark finding, presented at IDWeek 2025, isn’t a reason to shy away from these revolutionary cancer treatments – but it’s a critical wake-up call for clinicians and, crucially, pharmacists. The future of myeloma treatment hinges on minimizing these risks through targeted prevention and vigilant monitoring.
The Evolving Landscape of Myeloma Treatment
Chimeric Antigen Receptor (CAR) T-cell therapy and bispecific antibodies (BsAbs) have dramatically altered the treatment paradigm for multiple myeloma, offering durable remissions and improved quality of life for many. These therapies harness the power of the immune system to target and destroy cancer cells. However, this potent immune activation comes at a cost: increased susceptibility to infections and a range of immune-related complications. Understanding the nuances of these risks is paramount.
IDWeek 2025: A Deep Dive into Infection Rates
A retrospective pharmacovigilance study utilizing the FDA Adverse Event Reporting System (FAERS) database compared infection incidence in patients treated with CAR-T therapies (Ciltacabtagene and Idecabtagene) and BsAbs (Teclistamab, Talquetamab, and Elranatanab). The results revealed a statistically significant difference: 32.2% of BsAb recipients experienced infections and immune dysregulation compared to 14.4% of those receiving CAR-T therapy (P < .01). This doesn’t mean CAR-T is ‘safer’ overall, but the *types* of infections and their association with severe immune events differ significantly.
Distinct Immune Risk Profiles
In the CAR-T cohort, hypogammaglobulinemia – a deficiency in antibodies – was the most frequent infection-related complication (1.31%), followed closely by fungal infections (1.20%). BsAb-treated patients, however, were more likely to contract cytomegalovirus (CMV) infections (1.79%), with hypogammaglobulinemia also prevalent (1.58%). These variations underscore the need for tailored prophylactic strategies based on the specific therapy administered. A one-size-fits-all approach simply won’t suffice.
The Critical Link Between Immune Complications and Infection
Perhaps the most concerning finding was the stronger association between infections and immune complications – Cytokine Release Syndrome (CRS), Immune-Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and Immune-Effector Cell-Associated Hemophagocytic Lymphohistiocytosis (IECHLH) – in CAR-T recipients. Infections occurred in conjunction with these syndromes in 20.0% of CAR-T patients versus only 6.1% of those on BsAbs (P < .01). This highlights the heightened vulnerability of patients experiencing these potentially life-threatening immune reactions. The study’s forest plot visually demonstrated the substantial impact of these events on infection risk and patient outcomes.
Pharmacists: Frontline Defenders Against Infection
Infections remain the leading cause of non-relapse mortality in myeloma patients undergoing these advanced therapies. This places pharmacists at the center of patient care. Their role extends far beyond dispensing medications. Pharmacists are uniquely positioned to:
- Assess individual patient risk factors for infection.
- Guide antimicrobial selection and dosing adjustments, particularly crucial in immunocompromised patients.
- Monitor for early signs of infection and immune-mediated complications.
- Collaborate with hematologists and infectious disease specialists to optimize treatment plans.
Proactive antimicrobial stewardship, informed by a deep understanding of the specific therapy’s immune profile, is no longer optional – it’s essential.
Looking Ahead: The Need for Consensus Guidelines and Personalized Approaches
As the use of CAR-T and BsAb therapies expands, the need for standardized, evidence-based guidelines for infection prevention and management becomes increasingly urgent. Current practices are largely based on expert opinion, and a lack of consensus can lead to inconsistent care. Future research should focus on identifying biomarkers that can predict infection risk and tailoring prophylactic strategies accordingly. We may see the development of more targeted immunomodulatory therapies to mitigate the severity of CRS, ICANS, and IECHLH, thereby reducing the associated infection risk. Furthermore, advancements in rapid diagnostic testing for opportunistic infections will be critical for timely intervention.
The promise of CAR-T and BsAb therapies is undeniable, but realizing their full potential requires a concerted effort to address the challenges posed by infection and immune dysregulation. Interdisciplinary collaboration, proactive monitoring, and a commitment to personalized medicine will be key to ensuring the safety and efficacy of these transformative treatments. What strategies are *you* implementing to mitigate these risks in your practice? Share your insights in the comments below!
