Overview: Why Immune Complications Matter in Advanced Multiple Myeloma Therapies
Chimeric Antigen Receptor (CAR-T) cell therapy and bispecific antibodies (BsAbs) have transformed the treatment landscape for multiple myeloma (MM), offering deep and durable responses for patients with relapsed or refractory disease. Yet, these immune-based therapies also bring new challenges. Immune complications, including impaired humoral and cellular immunity, can elevate the risk of infections at multiple points during and after treatment. Understanding these risks is essential for patients, caregivers, and clinicians aiming to maximize benefits while preventing serious infections.
How CAR-T and BsAb Therapies Alter Immune Function
CAR-T therapy uses patient-derived T cells engineered to recognize a myeloma-associated antigen. BsAbs simultaneously bind a myeloma cell and a T cell to redirect cytotoxic activity. Both approaches can dramatically reshape the immune system:
- B-cell aplasia and hypogammaglobulinemia: Targeted therapies can disrupt normal B-cell development and immunoglobulin production, reducing antibody diversity and weakening humoral immunity. This leaves patients more susceptible to bacterial infections, particularly in the first months after therapy.
- Neutropenia and cellular immune changes: Cytopenias and altered T-cell dynamics can compromise innate and adaptive responses, increasing susceptibility to viral, fungal, and bacterial pathogens.
- Cytokine release and inflammatory sequelae: Severe immune activation can trigger cytokine release syndrome (CRS) and neurotoxicity, which may necessitate treatments that temporarily dampen immunity, further elevating infection risk.
Infections in this context are not only a function of pathogens but also the treatment window. The highest risk often occurs during the first 1–2 months post-infusion, but feelings of fatigue and ongoing immune suppression can persist for many months, especially in patients with prior lines of therapy or impaired organ function.
Patterns of Infection: What Clinicians See
Data from clinical trials and real-world experience show:
- Early infections frequently involve respiratory bacteria and viruses, leading to pneumonia-like illnesses or flu-like symptoms that require prompt evaluation.
- Late infections may reflect prolonged hypogammaglobulinemia, with bacterial sinopulmonary infections and, less commonly, opportunistic pathogens in patients with sustained immune suppression.
- Fungal infections, although less common, can occur in patients with severe neutropenia or prolonged immunosuppression, particularly after repeated therapies or in those with diabetes or other comorbidities.
Recognizing fever, new respiratory symptoms, or unusual fatigue early is crucial, as infections can rapidly progress in immunocompromised patients.
Prevention and Management Strategies
Effective management hinges on a combination of risk assessment, prophylaxis, and timely treatment:
- <strongInfection risk assessment: Before therapy, evaluate prior infections, comorbidities, vaccination status, and baseline immunoglobulin levels. Ongoing monitoring includes regular blood counts and infectious disease screening when indicated.
- <strongVaccination and immune support: Vaccination strategies should be aligned with current guidelines for MM patients. In many cases, clinicians consider administering inactivated vaccines when immune recovery permits. For patients with sustained hypogammaglobulinemia, immunoglobulin replacement therapy (IVIG or subcutaneous IG) can reduce bacterial infection risk and hospitalization.
- <strongAntimicrobial prophylaxis: Depending on risk factors and local patterns of resistance, prophylactic antibiotics, antifungals, or antivirals may be recommended during peak vulnerability periods.
- <strongPrompt treatment of infections: Early empiric therapy is often initiated at the first sign of infection in high-risk individuals, with adjustments based on culture results and imaging findings.
- <strongTherapy adjustments: In some cases, clinicians may modify CAR-T or BsAb dosing or schedule to balance disease control with infection risk, especially in patients with significant cytopenias or organ dysfunction.
Overall, a multidisciplinary approach—including hematology, infectious disease, pharmacy, and primary care—helps tailor a prevention and treatment plan to each patient’s unique immune status and disease trajectory.
Patient Guidance: What to Ask Your Care Team
Patients and families can play a key role in mitigating infection risk by engaging with the care team on:
- Vaccination planning and timing
- Recognizing early infection symptoms and fever thresholds
- Adherence to prophylaxis and monitoring schedules
- Signs of graft-versus-host-like effects in related contexts, and when to seek care
With careful monitoring and proactive prevention, the infection risks associated with immune-based MM therapies can be managed effectively, enabling more patients to benefit from the remarkable disease control these therapies offer.
