This is a micro-learning module summary of a presentation by Dr Ajay Nooka which you can find here. Before participating, please read our CME and disclosure information which can be found here.
This activity is supported by an independent medical educational grant from Johnson & Johnson. This online education program has been designed for US Healthcare Professionals.
While BCMA-targeting bispecific antibodies (BsAbs) demonstrate robust efficacy and durable responses in relapsed/refractory multiple myeloma (RRMM), they are associated with a significantly higher incidence of severe infectious complications than CAR-T or GPRC5D-directed therapies. Because viral and respiratory infections peak within the first few months of treatment, proactive, longitudinal infection mitigation is essential for ensuring patient safety and treatment continuity.
Baseline Screening and Pre-treatment Protocols
- Viral Screening: Prior to initiating BsAb therapy, all patients must be comprehensively screened for Hepatitis B (HBV), Hepatitis C (HCV), HIV, CMV, EBV and COVID-19.
- Vaccinations: Patients must be fully up to date with all standard and seasonal vaccinations, specifically including influenza, RSV, and COVID-19, before beginning treatment.
- Active Infections: BsAb therapy MUST NOT be initiated in any patient currently battling an active infection.
Immunoglobulin Replacement Therapy (IVIG)
- Hypogammaglobulinemia Management: BCMA-directed therapies reliably induce B-cell aplasia and profound hypogammaglobulinemia. Consequently, routine intravenous immunoglobulin (IVIG) replacement is considered mandatory.
- Target Levels: IVIG should be administered prophylactically to maintain serum IgG levels at or above 400 mg/dL. Among patients with IgG isotype myeloma, it becomes tricky as the abnormal IgG interferes with the IgG quantification – would recommend IVIG replacement in everyone irrespective of the IgG levels.
- Clinical Impact: Consistent IgG replacement significantly mitigates infection risk, demonstrating up to an 80% reduction in grade 3 or higher infections in retrospective analyses. Furthermore, clinical trial data explicitly links fatal infections to the absence of IVIG prophylaxis.
Standard Antimicrobial and Antiviral Prophylaxis
- Viral Prophylaxis: Routine, continuous administration of valcyclovir (e.g., 500mg daily) or acyclovir 400mg PO BID is required to prevent herpes simplex virus (HSV) and varicella-zoster virus (VZV) reactivation.
- PJP Prophylaxis: Patients must receive continuous prophylaxis to prevent Pneumocystis jirovecii pneumonia (PJP), typically utilizing Bactrim (e.g., single strength daily or double strength Monday/Wednesday/Friday).
Longitudinal Dose Optimization and Supportive Care
- Dose Spacing: Prolonged weekly administration is associated with cumulative infection risks. Transitioning patients to every-two-week (Q2W) or every-four-week (Q4W) dosing schedules after achieving a strong response (such as a Very Good Partial Response, or VGPR) substantially reduces the incidence of new-onset grade 3 and 4 infections over time.
- Growth Factors: The use of growth factors, such as G-CSF, is not contraindicated alongside BsAbs or tocilizumab. They should be utilized liberally to manage grade 3 or higher neutropenia accompanied by fever, or isolated grade 4 neutropenia.
- Administration Timing: Clinicians should aim to maintain an absolute neutrophil count (ANC) greater than 1000. However, growth factors should not be administered during the step-up dosing phase or during active cytokine release syndrome (CRS).
Content is accurate as of the date of release.