Tecvayli - Drug Monograph

Introduction

Tecvayli (teclistamab-cqyv) is a first-in-class bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager approved by the FDA in October 2022. It represents a significant advancement in the treatment of relapsed or refractory multiple myeloma, offering a novel immunotherapeutic approach for patients who have exhausted multiple prior lines of therapy.

Mechanism of Action

Tecvayli is a bispecific antibody that simultaneously binds to BCMA expressed on multiple myeloma cells and CD3 expressed on T-cells. This dual binding facilitates the formation of an immunological synapse between T-cells and multiple myeloma cells, resulting in:

• T-cell activation and proliferation
• Cytokine release
• Direct cytotoxic activity against BCMA-expressing cells
• Lysis of multiple myeloma cells through perforin and granzyme-mediated pathways

The drug redirects CD3-positive T-cells to engage and eliminate BCMA-positive multiple myeloma cells, independent of MHC recognition or T-cell receptor specificity.

Indications

Tecvayli is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Dosage and Administration

• Step-up dose 1: 0.06 mg/kg subcutaneous injection
• Step-up dose 2: 0.3 mg/kg subcutaneous injection (2-4 days after first step-up dose)
• First treatment dose: 1.5 mg/kg subcutaneous injection (3-5 days after second step-up dose)

• 1.5 mg/kg subcutaneous injection weekly until disease progression or unacceptable toxicity

• Administer in a healthcare setting equipped to manage cytokine release syndrome (CRS)
• Premedicate with corticosteroids, antihistamines, and antipyretics
• Monitor patients for ≥48 hours after each step-up dose and first treatment dose

• Renal impairment: No dosage adjustment recommended
• Hepatic impairment: No dosage adjustment recommended for mild to moderate impairment; not studied in severe impairment
• Elderly: No dosage adjustment recommended

Pharmacokinetics

• Bioavailability: ~65% following subcutaneous administration
• Time to peak concentration: 2-4 days post-dose

• Volume of distribution: ~6.5 L
• Plasma protein binding: Not extensively bound to plasma proteins

• Primarily metabolized via proteolytic degradation pathways
• No significant cytochrome P450-mediated metabolism

• Half-life: ~4-9 days
• Clearance: ~0.5 L/day
• Excretion: Primarily through catabolism to small peptides and amino acids

Contraindications

• History of severe hypersensitivity to teclistamab or any of its excipients
• Active infection not adequately controlled
• Concurrent use with other BCMA-directed therapies

Warnings and Precautions

• Occurred in 72% of patients in clinical trials
• May be life-threatening or fatal
• Requires monitoring and management according to institutional protocols
• Tocilizumab should be available for treatment of CRS

• Immune effector cell-associated neurotoxicity syndrome (ICANS) reported in patients
• Includes encephalopathy, motor dysfunction, and cranial nerve palsies
• Monitor for signs and symptoms of neurologic toxicity

• Increased risk of serious and opportunistic infections
• Prophylaxis for herpes simplex virus, Pneumocystis jirovecii pneumonia, and other infections recommended
• Monitor for signs and symptoms of infection throughout treatment

• Neutropenia, anemia, and thrombocytopenia commonly reported
• Monitor complete blood counts regularly
• Supportive care with growth factors and transfusions as needed

• Elevations in liver enzymes reported
• Monitor liver function tests regularly

Drug Interactions

• May enhance immunosuppressive effects and increase infection risk
• Consider withholding concomitant immunosuppressants during treatment

• May decrease exposure to CYP450 substrates due to cytokine-mediated suppression of enzyme activity
• Monitor drugs with narrow therapeutic indices

• Contraindicated during treatment and until immune recovery
• Inactivated vaccines may have reduced efficacy

Adverse Effects

• Cytokine release syndrome (72%)
• Fatigue (50%)
• Fever (40%)
• Musculoskeletal pain (35%)
• Injection site reactions (32%)
• Nausea (30%)
• Diarrhea (25%)
• Neutropenia (64%)
• Anemia (40%)
• Thrombocytopenia (30%)

• Severe infections (including COVID-19, pneumonia)
• Neurologic toxicity (including ICANS)
• Hepatic toxicity
• Severe cytopenias

Monitoring Parameters

• Complete blood count with differential
• Comprehensive metabolic panel
• Infectious disease screening
• Neurologic assessment

• Daily monitoring for CRS symptoms during step-up dosing period
• Regular CBC (at least weekly for first month)
• Liver function tests regularly
• Signs and symptoms of infection
• Neurologic assessment at each visit
• Response assessment per IMWG criteria

• Immunoglobulin levels
• T-cell subsets
• Minimal residual disease assessment
• Bone marrow evaluations

Patient Education

• Explain the need for hospitalization during initial doses
• Describe potential side effects, particularly CRS symptoms
• Emphasize importance of reporting any new symptoms immediately

• Practice good hand hygiene
• Avoid crowds and sick individuals
• Report any signs of infection promptly

• Educate about fever, chills, hypotension, and other CRS symptoms
• Provide emergency contact information
• Explain the management plan for CRS

• Importance of maintaining weekly dosing schedule
• Proper injection technique if self-administered (after appropriate training)
• Never miss scheduled appointments

• Avoid alcohol consumption
• Maintain adequate hydration
• Follow a balanced diet to support immune function

References

1. FDA Prescribing Information: Tecvayli (teclistamab-cqyv). October 2022. 2. Moreau P, et al. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2022;387(6):495-505. 3. Usmani SZ, et al. Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, in relapsed or refractory multiple myeloma: phase 1 results. J Clin Oncol. 2022;40(16_suppl):8008. 4. National Comprehensive Cancer Network (NCCN) Guidelines Multiple Myeloma. Version 3.2023. 5. ClinicalTrials.gov: MajesTEC-1 study (NCT04557098). 6. American Society of Clinical Oncology (ASCO) Guidelines for Multiple Myeloma. 2022. 7. European Hematology Association (EHA) Guidelines for Multiple Myeloma. 2021.