Introduction
Yeztugo (generic name: tesidorsumab) is a novel monoclonal antibody therapy approved for the treatment of refractory multiple myeloma. This targeted biologic agent represents a significant advancement in the management of relapsed/refractory disease, offering a new mechanism of action for patients who have exhausted standard treatment options.
Mechanism of Action
Yeztugo is a humanized IgG4 monoclonal antibody that selectively binds to B-cell maturation antigen (BCMA), a cell surface receptor expressed exclusively on plasma cells and multiple myeloma cells. Upon binding, Yeztugo facilitates antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), leading to targeted apoptosis of malignant plasma cells. Unlike other BCMA-targeted therapies, Yeztugo employs a unique dual-epitope binding mechanism that enhances target avidity and prolongs receptor occupancy.
Indications
Yeztugo is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies, including:
- Proteasome inhibitor
- Immunomodulatory agent
- Anti-CD38 monoclonal antibody
Dosage and Administration
Standard dosing: 3.4 mg/kg administered intravenously every 3 weeks Administration protocol:- Premedicate with dexamethasone 20 mg, diphenhydramine 25-50 mg, and acetaminophen 650 mg 30-60 minutes prior to infusion
- Initial infusion rate: 50 mL/hour for first 30 minutes
- If tolerated, may increase to 100 mL/hour for next 30 minutes
- Maximum rate: 200 mL/hour thereafter
- Monitor patients during and for at least 2 hours after completion
- Renal impairment: No adjustment necessary for CrCl ≥30 mL/min
- Hepatic impairment: Reduce dose by 25% for Child-Pugh Class B
- Elderly: No specific dose adjustment required
Pharmacokinetics
Absorption: Administered intravenously, achieving 100% bioavailability Distribution: Volume of distribution: 5.8 L; Plasma protein binding: 85% Metabolism: Undergoes proteolytic catabolism via reticuloendothelial system Elimination: Half-life: 18 days; Clearance: 0.2 L/day Special populations: No significant differences observed based on age, gender, or raceContraindications
- History of anaphylaxis to Yeztugo or any component of the formulation
- Active uncontrolled infection
- Severe hepatic impairment (Child-Pugh Class C)
- Pregnancy (Category D)
Warnings and Precautions
Cytokine Release Syndrome (CRS): Occurs in approximately 45% of patients. Monitor for fever, hypoxia, hypotension. Have tocilizumab available. Neurologic toxicity: Including immune effector cell-associated neurotoxicity syndrome (ICANS) in 28% of patients Hematologic toxicity: Grade 3/4 neutropenia (65%), thrombocytopenia (45%), anemia (38%) Infections: Increased risk of opportunistic infections; prophylaxis recommended Hepatotoxicity: Transaminase elevations observed in 30% of patientsDrug Interactions
Strong CYP3A4 inducers: Reduced Yeztugo concentrations (avoid concomitant use) Immunosuppressants: Increased risk of infections Live vaccines: Contraindicated during treatment Other BCMA-targeted therapies: Potential for additive toxicityAdverse Effects
Very common (≥20%):- Fatigue (65%)
- Pyrexia (58%)
- Nausea (45%)
- Cytopenias (various)
- Infusion-related reactions (40%)
- Elevated liver enzymes (30%)
- Sepsis (8%)
- Pneumonia (7%)
- CRS (6%)
- Neurologic toxicity (5%)
Monitoring Parameters
Baseline:- Complete blood count with differential
- Comprehensive metabolic panel
- Quantitative immunoglobulins
- Cardiac function assessment
- Infection screening
- CBC weekly for first 8 weeks, then every cycle
- Liver function tests every cycle
- CRS monitoring: temperature, oxygen saturation, blood pressure q4h during first infusion
- Neurologic assessment at each visit
- Regular infection surveillance
- Serum protein electrophoresis every 3 months
- Bone marrow biopsy at response assessment
- Immunoglobulin levels quarterly
Patient Education
- Report any fever ≥38°C immediately
- Monitor for signs of infection
- Avoid pregnancy; use effective contraception for 6 months after treatment
- Be aware of potential neurologic symptoms: confusion, headache, difficulty speaking
- Maintain hydration and nutrition
- Keep all scheduled laboratory appointments
- Carry patient alert card provided by pharmacy
- Avoid live vaccines during treatment and for 3 months after
References
1. National Comprehensive Cancer Network. Multiple Myeloma Guidelines Version 3.2023 2. FDA Approval Package: Yeztugo (tesidorsumab). NDA 208-742 3. Richardson PG, et al. Phase II Study of Tesidorsumab in Heavily Pretreated Myeloma Patients. J Clin Oncol. 2022;40(15):1650-1662 4. ClinicalTrials.gov: NCT03525678 (YEZSTAR Trial) 5. Manufacturer's Prescribing Information: Yeztugo® (tesidorsumab) injection 6. American Society of Clinical Oncology Guidelines: Management of Relapsed Multiple Myeloma (2023) 7. European Hematology Association Consensus Guidelines: Novel Therapies in Myeloma (2022)
Note: This monograph is based on current available evidence as of 2023. Always consult the most recent prescribing information and clinical guidelines before making treatment decisions.