Usage
Teclistamab is prescribed for the treatment of adult patients with relapsed or refractory multiple myeloma. These patients must have received at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy. It belongs to the pharmacological class of antineoplastic agents, specifically bispecific T-cell engager (BiTE) antibodies. Teclistamab’s mechanism of action involves binding to both CD3 receptors on T-cells and B-cell maturation antigen (BCMA) on myeloma cells. This dual binding redirects T-cells to kill myeloma cells.
Alternate Names
Teclistamab is also known by the brand name Tecvayli.
How It Works
Pharmacodynamics: Teclistamab causes T-cell activation and cytokine release, leading to myeloma cell death. This can also result in cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
Pharmacokinetics: Teclistamab is administered subcutaneously. It exhibits approximately dose-proportional pharmacokinetics. The mean bioavailability is around 72%. Ninety percent of steady-state exposure is achieved after 12 weekly doses. It is not extensively metabolized by CYP450 enzymes. Elimination pathways and the exact half-life are not fully characterized.
Mode of Action: Teclistamab is a BiTE antibody that binds to both CD3 on T cells and BCMA on myeloma cells. This simultaneous binding activates T cells, triggering the release of cytotoxic granules and cytokines, leading to myeloma cell lysis.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: The primary mode of action involves receptor binding (CD3 and BCMA). It does not involve direct enzyme inhibition or neurotransmitter modulation.
Elimination Pathways: Elimination pathways are not explicitly described in the available summaries.
Dosage
Standard Dosage
Adults:
The standard dosage is 1.5 mg/kg administered subcutaneously once weekly. Prior to initiating weekly dosing, a step-up dosing schedule is required:
- Step-up dose 1: 0.06 mg/kg subcutaneously on Day 1.
- Step-up dose 2: 0.3 mg/kg subcutaneously on Day 4 (2-7 days after dose 1).
- First treatment dose: 1.5 mg/kg subcutaneously on Day 7 (2-7 days after dose 2).
Patients who achieve and maintain a complete response for at least six months may be eligible for a reduced dosing frequency of 1.5 mg/kg every two weeks.
Children:
The safety and efficacy of Teclistamab in children have not been established.
Special Cases:
- Elderly Patients: No dose adjustment is required.
- Patients with Renal Impairment: No dose adjustment is recommended for mild or moderate renal impairment. Limited data exists for severe renal impairment.
- Patients with Hepatic Dysfunction: No dose adjustment is recommended for mild hepatic impairment. No data are available for moderate or severe hepatic impairment.
- Patients with Comorbid Conditions: Caution is advised in patients with pre-existing neurological conditions or a history of stroke or seizure.
Clinical Use Cases
Dosage recommendations for intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations are not specified as Teclistamab is specifically indicated for relapsed/refractory multiple myeloma.
Dosage Adjustments
Dose modifications may be necessary based on adverse events. See below:
- CRS: Temporarily withhold Teclistamab until resolution.
- ICANS: Temporarily withhold Teclistamab until resolution.
- Neutropenia: Withhold Teclistamab until absolute neutrophil count recovers.
- Thrombocytopenia: Withhold Teclistamab until platelet count recovers.
- Other Grade 3 or 4 adverse reactions: Withhold Teclistamab until the reaction improves to Grade 2 or less.
Side Effects
Common Side Effects:
Cytokine release syndrome (CRS), musculoskeletal pain, injection site reactions, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, diarrhea, decreased white blood cells, decreased hemoglobin, decreased platelets.
Rare but Serious Side Effects:
Severe CRS, immune effector cell-associated neurotoxicity syndrome (ICANS), severe infections.
Long-Term Effects:
Long-term effects are not fully characterized. Hypogammaglobulinemia has been observed.
Adverse Drug Reactions (ADR):
Clinically significant ADRs primarily include CRS and ICANS, which require prompt management.
Contraindications
Hypersensitivity to Teclistamab or any of its components. Active infection during step-up dosing.
Drug Interactions
No formal drug interaction studies have been performed. However, the initial release of cytokines may transiently suppress CYP450 enzyme activity. Monitor patients receiving concomitant CYP450 substrates, especially those with a narrow therapeutic index.
Pregnancy and Breastfeeding
Teclistamab is not recommended during pregnancy and breastfeeding. Effective contraception is necessary during treatment and for five months after the last dose for women and three months after the last dose for men. Breastfeeding is contraindicated during treatment and for five months after the last dose.
Drug Profile Summary
- Mechanism of Action: BiTE antibody binding to CD3 on T cells and BCMA on myeloma cells, redirecting T cells to kill myeloma cells.
- Side Effects: CRS, musculoskeletal pain, injection site reactions, fatigue, infections, cytopenias. Serious side effects: severe CRS, ICANS.
- Contraindications: Hypersensitivity, active infection during step-up dosing.
- Drug Interactions: Potential for interaction with CYP450 substrates due to transient cytokine-mediated enzyme suppression.
- Pregnancy & Breastfeeding: Not recommended. Contraceptive measures are necessary.
- Dosage: 1.5 mg/kg SC weekly after step-up dosing.
- Monitoring Parameters: Complete blood counts, signs and symptoms of CRS and ICANS, liver function tests.
Popular Combinations
Teclistamab is being investigated in combination with other agents, including daratumumab, pomalidomide, bortezomib, and dexamethasone.
Precautions
Screen for allergies, infections, and pre-existing neurological conditions. Close monitoring for CRS and ICANS is crucial, particularly during the step-up dosing phase. Avoid live virus vaccinations.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Teclistamab?
A: 1.5 mg/kg subcutaneously once weekly following a step-up dosing schedule (0.06 mg/kg on Day 1, 0.3 mg/kg on Day 4).
Q2: What is the mechanism of action of Teclistamab?
A: It’s a BiTE antibody targeting CD3 on T-cells and BCMA on myeloma cells, facilitating T-cell mediated myeloma cell death.
Q3: What are the most common side effects?
A: CRS, musculoskeletal pain, injection site reactions, fatigue, upper respiratory tract infections, and cytopenias.
Q4: What are the serious side effects to watch for?
A: Severe CRS, ICANS, and severe infections.
Q5: What are the contraindications to Teclistamab?
A: Hypersensitivity to the drug or its components and active infections during the step-up dosing phase.
Q6: Can Teclistamab be used in pregnant or breastfeeding women?
A: No, it is not recommended due to potential fetal harm and unknown effects on infants.
Q7: Are there any drug interactions I should be aware of?
A: The initial cytokine release may suppress CYP450 activity, potentially affecting drugs metabolized by these enzymes.
Q8: What monitoring is recommended during Teclistamab treatment?
A: Monitor for signs and symptoms of CRS and ICANS, complete blood counts, and liver function.
Q9: How is Teclistamab administered?
A: Subcutaneously.
Q10: Can the dosing frequency of Teclistamab be reduced?
A: Yes, for patients who maintain complete response for a minimum of 6 months, the frequency can be reduced to every two weeks.
