Understanding the Shift in Multiple Myeloma Treatment
Advances in multiple myeloma (MM) have ushered in a new era of immunotherapies, notably Chimeric Antigen Receptor (CAR) T-cell therapy and bispecific antibody (BsAb) therapy. These approaches leverage the patient’s own immune system to target myeloma cells, often achieving deep and lasting responses where traditional therapies fall short. Yet with this promise comes a heightened concern: immune complications that can elevate infection risk, particularly in patients with advanced disease. This article examines why immune complications arise with these therapies, how they influence infection risk, and what clinicians and patients can do to mitigate danger while preserving therapeutic benefit.
Why Immune Complications Occur with CAR T-Cell and BsAb Therapies
CAR T-cell therapy involves engineering a patient’s T cells to recognize a myeloma-associated antigen, then infusing them back to seek and destroy malignant cells. BsAbs, on the other hand, recruit T cells to cancer cells by binding both, facilitating immune synapse formation. In both strategies, potent immune activation is a feature, not a side effect. While this immune engagement can drive tumor control, it can also lead to cytopenias, hypogammaglobulinemia, and dysregulated immune responses.
Two prevalent immune-related challenges are cytokine release syndrome (CRS) and neurotoxicity, which often occur early after infusion. Beyond these acute events, patients may experience prolonged immune suppression, especially when prior lines of therapy have already compromised bone marrow reserve. The net effect is an increased susceptibility to bacterial, viral, and fungal infections during and after treatment, with risk spanning days to months depending on the therapy, disease burden, and baseline immune function.
Infection Risk in Advanced MM: What the Data Show
Infection is a leading cause of morbidity in MM, and its risk profile shifts with immunotherapies. Early post-infusion periods can see higher rates of febrile episodes and pneumonia, while later phases may involve recurrent viral reactivations or opportunistic infections in patients with prolonged cytopenias or hypogammaglobulinemia. Studies suggest that infection risk correlates with several factors: disease stage, prior therapies, intensity of lymphodepletion, and the duration of immune cell reconstitution. Importantly, even patients who achieve deep remissions with CAR T or BsAb therapy may face persistent vulnerability if immune function takes longer to recover.
Strategies to Mitigate Infection Risk
Mitigating infection risk requires a multi-pronged approach that starts before therapy and extends through the recovery period:
- <strongPre-treatment assessment: Evaluate baseline immune status, comorbidities, and prior infections. Vaccination status should be reviewed, and non-immunosuppressive strategies favored when possible.
- <strongInfection prophylaxis: Prophylactic antibiotics, antifungals, or antivirals may be indicated based on institutional protocols and patient risk. IgG replacement therapy may be considered for those with significant hypogammaglobulinemia.
- <strongMonitoring and early intervention: Close clinical surveillance for fever, respiratory symptoms, and signs of sepsis is essential. Regular blood counts and inflammatory markers help detect deterioration early.
- <strongSupportive care: Growth factors can aid neutrophil recovery in selected patients, and prompt management of CRS or neurotoxicity helps reduce downstream infectious complications.
- <strongVaccination planning: Vaccines should be administered when immune reconstitution allows, often after stabilization post-therapy, to maximize protective responses without compromising safety.
Communication among hematologists, infectious disease specialists, and primary care teams is critical. Individualized risk assessment guides the intensity and duration of prophylaxis, balancing infection prevention with the goal of maintaining anti-meloma efficacy.
Patient-Centered Considerations
Educating patients about infection signs, limiting exposure to crowded environments during peak risk periods, and adhering to prescribed prophylaxis can shift the balance toward safer outcomes. Shared decision-making is essential when weighing the benefits of continued immunotherapy against potential infectious complications, especially in later lines of therapy where bone marrow reserve may be limited.
Looking Ahead
Ongoing research aims to refine CAR T-cell and BsAb platforms to maintain anti-mmyeloma activity while reducing unintended immune suppression. Innovative strategies include optimizing lymphodepletion regimens, developing more controllable CAR constructs, and improving infection surveillance with biomarker-guided approaches. As the field evolves, so too will the standard of care for preventing and treating infections in patients receiving these transformative therapies.
