Managing Bispecific Toxicities: Proactive Strategies for CRS and Infections
An expert explains that while bispecific antibodies show strong efficacy in relapsed/refractory multiple myeloma, optimizing their safety—through step-up dosing, infection prophylaxis, immunoglobulin support, and early symptom management—is essential to minimizing toxicity and expanding access to this promising treatment class.
EP: 1.Understanding REALiTEC: Real-World Insights on BCMA Bispecifics
EP: 2.Teclistamab in Practice: Real-World Efficacy and Infection Risks
EP: 3.Exploring Bispecific Combinations: REDIRECTT ASCO 2025 Highlights
EP: 4.Managing Bispecific Toxicities: Proactive Strategies for CRS and Infections
Bispecific antibody therapy in relapsed/refractory multiple myeloma has shown promising efficacy, but safety remains a critical consideration—especially regarding cytokine release syndrome (CRS) and infections. Fortunately, CRS and neurotoxicity tend to be mild and occur early in treatment. Step-up dosing is a commonly used strategy to mitigate these risks. Some institutions also use preemptive tocilizumab to further reduce CRS incidence. A simpler approach involves initiating therapy with the bispecific agent and managing symptoms such as fever with dexamethasone, which can often prevent progression and reduce the need for hospitalization or additional interventions. These approaches are applicable to bispecifics targeting both BCMA and GPRC5D.
Beyond early toxicities, a greater long-term concern is the risk of infection due to immunosuppression. To minimize this, patients should be current on age-appropriate immunizations, including vaccines for influenza, COVID-19, pneumococcus, Haemophilus influenzae, and respiratory syncytial virus in older adults. Antiviral prophylaxis, typically with acyclovir or valacyclovir, helps protect against herpes viruses, while Pneumocystis jirovecii pneumonia prophylaxis with trimethoprim-sulfamethoxazole is standard. Alternatives such as dapsone, atovaquone, or nebulized pentamidine can be used in cases of allergy or intolerance.
Many patients with relapsed/refractory disease also experience hypogammaglobulinemia. For those with low IgG levels—especially below 400 mg/dL—immunoglobulin replacement therapy is often considered, either intravenously or subcutaneously. Even in patients without prior infections, low IgG levels may warrant prophylactic intravenous immunoglobulin depending on clinical judgment. Education plays a key role: patients are advised to report symptoms of respiratory or gastrointestinal illness promptly for early evaluation and treatment. With these comprehensive supportive care strategies, the safety profile of bispecific therapies can be optimized, allowing broader access and improved outcomes for patients with multiple myeloma.
