Managing Infection Risks in BCMA Bispecific Antibody Therapy: Ajay K. Nooka, MD, MPH

Infections are a recognized complication when BCMA bispecific antibodies are administered for relapsed/refractory multiple myeloma, and they can be managed safely through specific clinical protocols, explains Ajay K. Nooka, MD, MPH, an investigator in the MajesTEC-3 trial (NCT05083169), professor in the Department of Hematology and Medical Oncology, director of the Myeloma Program, and associate director of clinical research at the Winship Cancer Institute, Emory University School of Medicine. Nooka spoke with The American Journal of Managed Care^® following the FDA’s decision to grant full approval to teclistamab (Tecvayli) and approval for its use with daratumumab hyaluronidase-fihj (Darzalex Faspro), both from Janssen Biotech.

Historically, data showed grade 3-4 infections—defined as those requiring hospitalization—affecting 50% to 60% of patients. Nooka contextualizes these high rates by noting they occurred during the COVID-19 pandemic, a period when the significant infection risk associated with these agents was not yet fully anticipated.

Insights from the MajesTEC-3 study clarified these risks, demonstrating that when BCMA bispecifics are combined with agents like daratumumab, the infection risk is not significantly higher than standard control arms. Consequently, Nooka argues that although infection risks are a “red flag,” they should not preclude the use of these therapies. Instead, clinicians must implement prophylactic “guardrails” to ensure patient safety.

A primary concern is hypogammaglobulinemia caused by total B-cell depletion, which can persist for 4 to 6 months after treatment ends. To mitigate this, Nooka recommends monthly intravenous immunoglobulin (IVIG) supplementation. Clinical trials, including MajesTEC-3, have shown that incorporating IVIG caused infection-related deaths to “drastically plummet” to near zero. Additionally, he advocates for the vigorous use of growth factors to prevent neutropenia, which frequently correlates with infection risks.

Clinical vigilance is essential, and Nooka advises that dosing must be withheld if a patient has a fever or active infection. Clinicians should maintain a low threshold for starting antibiotics, treating any fever as a potential infection to prevent rapid deterioration from gram-negative sepsis. Finally, regarding vaccinations, he suggests administering them before starting bispecific therapy if possible, although he still encourages vaccination during treatment to facilitate at least a partial immune response.