Overview: A New Frontier in Multiple Myeloma Treatment
Chimeric Antigen Receptor (CAR T-cell) therapy and bispecific antibody (BsAb) therapy have transformed the management of advanced multiple myeloma (MM). These immunotherapies mobilize the patient’s own immune system to target and destroy malignant plasma cells, offering durable responses for many who have exhausted conventional therapies. Yet, with this promise comes a unique set of immune challenges: immune suppression, dysregulated immune responses, and an elevated risk of infection. Understanding these risks is essential for patients, caregivers, and clinicians navigating advanced MM care.
Why Immune Complications Occur with CAR T-Cell and BsAb Therapies
CAR T-cell therapy engineers a patient’s T cells to recognize specific antigens on myeloma cells. After infusion, these modified cells proliferate and attack cancer cells, often producing remission. However, this immune activation can be accompanied by adverse events such as cytokine release syndrome (CRS) and neurotoxicity, which may necessitate intensive monitoring and temporary immunosuppression. In parallel, BsAb therapies bring two targets together: a myeloma cell and an immune effector, directing immune activity against the cancer. While BsAbs can produce rapid responses, they can also provoke B-cell depletion and broader immune perturbations, contributing to infection susceptibility. The net effect is an altered immune landscape that may leave patients more vulnerable to bacterial, viral, and fungal infections, especially in the early weeks to months after treatment.
The Infection Risk Profile in Advanced MM Immunotherapy
Infection risk with CAR T-cell and BsAb therapies is multifaceted. Neutropenia, hypogammaglobulinemia, and epithelial barrier disruption can reduce defense against pathogens. Antimicrobial prophylaxis, timely vaccination, and close clinical surveillance are critical components of care. Common infections observed include respiratory tract infections, bloodstream infections, and reactivations of latent viruses such as herpesviruses. The risk is typically highest during periods of peak immune reconstitution when T cells recover and normal immune balance is being reestablished. Individual risk factors—age, prior lines of therapy, comorbidities, and disease burden—also influence the likelihood and severity of infectious complications.
Neutropenia and Humoral Immunity Deficits
CAR T-cell therapy can cause transient cytopenias, including neutropenia, which reduces the first line of defense against bacterial infections. BsAb therapies may contribute to B-cell aplasia and hypogammaglobulinemia, impairing humoral immunity and antibody-mediated protection. Both scenarios necessitate proactive strategies to monitor white blood cell counts, immunoglobulin levels, and signs of infection. In some cases, immunoglobulin replacement therapy is considered to bolster humoral immunity and mitigate infection risk.
<h2Strategies to Mitigate Infection Risk
Prevention and early detection are cornerstones of care for patients undergoing advanced MM immunotherapies. Key approaches include:
- Risk stratification before, during, and after treatment to tailor monitoring and prophylaxis.
- Antimicrobial prophylaxis guided by institutional protocols and patient risk profiles.
- Regular screening for viral reactivations and prompt antiviral therapy when indicated.
- Vaccination planning, timed to align with immune recovery stages when appropriate.
- Timely management of neutropenia and consideration of growth factors when clinically appropriate.
- Early evaluation of fever or infection signs with rapid diagnostic testing and treatment initiation.
<h2What This Means for Patients and Care Teams
For patients, the prospect of long-lasting disease control must be balanced against infection risk and the potential need for additional therapies to manage immune complications. Empowering patients with education about infection symptoms, hygiene, and when to seek care is essential. For clinicians, multidisciplinary collaboration among hematologists, infectious disease specialists, pharmacists, and nursing teams is crucial to optimize prophylaxis, monitor adverse events, and adjust treatment plans in real time. Advances in supportive care—such as personalized infection prevention programs and real-time monitoring tools—are helping to reduce infection-related hospitalizations and improve overall outcomes.
<h2Looking Ahead: Research and Real-World Practice
Ongoing studies aim to refine risk prediction, develop safer immunotherapy regimens, and identify biomarkers that signal when infection risk is highest. Real-world data from diverse patient populations continue to inform best practices for prophylaxis and management, ensuring that the life-extending benefits of CAR T-cell and BsAb therapies can be realized with minimized infectious complications. Patients and clinicians should remain engaged in shared decision-making, weighing the potential for durable disease control against the need for vigilant infection prevention.
