General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

**REMS Drug**

Pronunciation:
tek-list-uh-mab

Trade Name(s)

• Tecvayli

Ther. Class.

antineoplastics

Pharm. Class.

T-cell engagers

Indications

Relapsed or refractory multiple myeloma in patients who have previously received ≥4 lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Action

Acts as a T-cell engager, binding to the CD3 receptor expressed on the surface of T-cells and B-cell maturation antigen expressed on the surface of multiple myeloma cells, resulting in facilitated lysis of malignant cells.

Therapeutic Effect(s):

Slowed progression of multiple myeloma.

Pharmacokinetics

Absorption: 72% absorbed following SUBQ administration.

Distribution: Not extensively distributed to tissues.

Metabolism and Excretion: Unknown.

Half-life: Unknown.

TIME/ACTION PROFILE (plasma concentrations)

Contraindication/Precautions

Contraindicated in:

• OB:   Pregnancy;
• Lactation:  Lactation.

Use Cautiously in:

• Rep:   Women of reproductive potential;
• Pedi:   Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: arrhythmia, edema, hypertension, hypotension

F and E: hypocalcemia, hyponatremia, hypophosphatemia

GI: constipation, diarrhea, HEPATOTOXICITY, hypoalbuminemia, nausea, vomiting

GU: acute kidney injury

Hemat: HEMORRHAGE, NEUTROPENIA, anemia, leukopenia, lymphopenia, thrombocytopenia

Local: injection site reactions

Metabolic: ↓ appetite

MS: pain

Neuro: encephalopathy, fatigue, headache, motor dysfunction, neuropathy, Guillain-Barré syndrome, IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME (ICANS), PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, SEIZURE

Resp: cough, hypoxia

Misc: CYTOKINE RELEASE SYNDROME (CRS), hypogammaglobulinemia, INFECTION, chills, fever, hypersensitivity reactions

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

May suppress activity of CYP450 drug-metabolizing enzymes (especially within 7 days after first dose and during/after onset of cytokine release syndrome); careful monitoring of  CYP450 substrates  is recommended.

Route/Dosage

SUBQ (Adults): Day 1 (step-up dose 1): 0.06 mg/kg as single dose;  Day 4 (step-up dose 2): 0.3 mg/kg as single dose;  Day 7 (1st treatment dose): 1.5 mg/kg as single dose;  Weekly dosing schedule: 1.5 mg/kg administered 1 wk after 1st treatment dose and then once weekly thereafter until disease progression or unacceptable toxicity. If patient achieves and maintains at least a complete response for ≥6 mo, may change to 1.5 mg/kg every 2 wk until disease progression or unacceptable toxicity.

Availability

Solution for SUBQ injection: 10 mg/mL, 90 mg/mL

Assessment

• Monitor for signs and symptoms of CRS (fever, hypoxia, chills, hypotension, sinus tachycardia, headache, ↑ liver enzymes). Hold therapy and administer supportive therapy for CRS; may include intensive care for severe or life-threatening CRS. Consider laboratory testing to monitor for disseminated intravascular coagulation and hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function. Grade 1 CRS:  If temperature ≥100.4°F,  hold teclistamab until CRS resolves. Administer pretreatment medications prior to next dose of teclistamab. Grade 2 CRS:  If temperature ≥100.4°F with hypotension responsive to fluids and not requiring vasopressors and/or oxygen requirement of low-flow nasal cannula or blow-by,  hold teclistamab until CRS resolves. Administer pretreatment medications prior to next dose. Hospitalize patients for 48 hr following the next dose of teclistamab. Grade 3 CRS:  If temperature ≥100.4°F with hypotension requiring one vasopressor with or without vasopressin and/or oxygen requirement of high-flow nasal cannula (>6 L/min), face mask, nonrebreather mask, or Venturi mask,  1st occurrence of Grade 3 CRS with duration <48 hr, hold teclistamab until CRS resolves. Provide supportive therapy, which may include intensive care. Administer pretreatment medications prior to next dose. Hospitalize patients for 48 hr following the next dose of teclistamab. For recurrent Grade 3 CRS or Grade 3 CRS with duration ≥48 hr, permanently discontinue teclistamab. Provide supportive therapy, which may include intensive care. Grade 4 CRS:  If temperature ≥100.4°F with hypotension requiring multiple vasopressors (excluding vasopressin) and/or oxygen requirement of positive pressure (continuous positive airway pressure, bilevel positive airway pressure, intubation, and mechanical ventilation),  permanently discontinue teclistamab. Provide supportive therapy, which may include intensive care.
• At the first sign of neurologic toxicity, including ICANS, hold teclistamab and consider neurology evaluation. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care, for severe or life-threatening neurologic toxicities, including ICANS. Neurologic toxicity, excluding ICANS,  Grade 1:  Hold teclistamab until neurologic toxicity symptoms resolve or stabilize.  Grade 2 or 1st occurrence of Grade 3:  Hold teclistamab until neurologic toxicity symptoms improve to ≤Grade 1. Provide supportive therapy.  Grade 3 (recurrent) or Grade 4:  Permanently discontinue teclistamab. Provide supportive therapy, which may include intensive care. ICANS,  Grade 1, depressed level of consciousness: awakens spontaneously:  Hold teclistamab until ICANS resolves. Monitor neurologic symptoms and consider consultation with neurologist for further evaluation and management, including consideration for starting nonsedating antiseizure medicines for seizure prophylaxis.  Grade 2, depressed level of consciousness: awakens to voice:  Hold teclistamab until ICANS resolves. Administer dexamethasone 10 mg IV every 6 hr. Continue dexamethasone until resolution to ≤Grade 1; then taper. Monitor neurologic symptoms and consider consultation with neurologist; consider starting nonsedating antiseizure medicines for seizure prophylaxis. Hospitalize patients for 48 hr following the next dose of teclistamab.  Grade 3, depressed level of consciousness: awakens only to tactile stimulus, or seizures (either any clinical seizure, focal or generalized, that resolves rapidly, or nonconvulsive seizures on electroencephalogram that resolve with intervention, or raised intracranial pressure: focal/local edema on neuroimaging): Administer dexamethasone 10 mg IV every 6 hr. Continue dexamethasone use until resolution to ≤Grade 1; then taper. Monitor neurologic symptoms and consider consultation with neurologist for further evaluation and management, including consideration for starting nonsedating antiseizure medicines for seizure prophylaxis. Provide supportive therapy, which may include intensive care. Hospitalize patients for 48 hr following the next dose of teclistamab.  Recurrent Grade 3 ICANS:  Discontinue teclistamab permanently. Administer dexamethasone 10 mg IV and repeat dose every 6 hr. Continue dexamethasone until resolution to ≤ Grade 1; then taper. Monitor neurologic symptoms and consider consultation with neurologist for further evaluation and management, including consideration for starting nonsedating antiseizure medicines for seizure prophylaxis. Provide supportive therapy, which may include intensive care.  Grade 4, depressed level of consciousness (either patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse), OR stupor or coma, or seizures (either life-threatening prolonged seizure [>5 min], or repetitive clinical or electrical seizures without return to baseline in between), OR motor findings (deep focal motor weakness [hemiparesis or paraparesis], OR ↑ intracranial pressure/cerebral edema, with signs/symptoms such as diffuse cerebral edema on neuroimaging, decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, or Cushing's triad:  Permanently discontinue teclistamab. Administer dexamethasone 10 mg IV and repeat dose every 6 hr. Continue dexamethasone until resolution to ≤Grade 1; then taper. Alternatively, consider administration of methylprednisolone 1000 mg per day IV and continue methylprednisolone 1000 mg per day IV for ≥2 days. Monitor neurologic symptoms and consider consultation with neurologist for further evaluation and management, including consideration for starting nonsedating antiseizure medicines for seizure prophylaxis. Provide supportive therapy, which may include intensive care.
• Monitor for signs and symptoms of infection.  For all grades of infection,  hold teclistamab in patients with active infection during the step-up dosing schedule.  For Grade 3 infections,  hold subsequent doses of until infection improves to ≤Grade 1.  For Grade 4 infections, consider permanent discontinuation of teclistamab. If not permanently discontinued, hold subsequent doses until infection improves to ≤Grade 1.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.

• Monitor liver enzymes and bilirubin at baseline and periodically during therapy. May cause ↑ AST and ALT. Hold teclistamab or consider permanent discontinuation of therapy.

Implementation

•  REMS: Teclistamab is available only through the Tecvayli and Talvey REMS due to the risk of CRS and neurologic problems. More information is available at https://www.tec-talrems.comor by calling 1-855-810-8064.
• Prior to starting therapy, consider initiation of antiviral prophylaxis to prevent herpes zoster reactivation per guidelines.
• Restarting teclistamab after dose delay:  Step-up dose 1:  If >7 days since last dose, restart teclistamab step-up dosing schedule at step-up dose 1 (0.06 mg/kg).  Step-up dose 2:  If 8–28 days since last dose, repeat step-up dose 2 (0.3 mg/kg) and continue teclistamab step-up dosing schedule. If >28 days since last dose, restart teclistamab step-up dosing schedule at step-up dose 1 (0.06 mg/kg).  For any treatment dose:  If ≤28 days since last dose, continue teclistamab at last treatment dose and schedule (1.5 mg/kg once weekly or 1.5 mg/kg every 2 wk). If >28 days since last dose, restart teclistamab step-up dosing schedule at step-up dose 1 (0.06 mg/kg).
• Patients should be hospitalized for 48 hr after all doses within the teclistamab step-up dosing schedule (1st treatment and step-up doses 1 and 2).
• Administer pretreatment medications (corticosteroid [PO or IV dexamethasone 16 mg], histamine-1 receptor antagonist [PO or IV diphenhydramine 50 mg], antipyretics [PO or IV acetaminophen 650 mg to 1000 mg]) prior to each dose of the teclistamab step-up dosing schedule.

Patient/Family Teaching

• Explain purpose and side effects of medication to patient. Advise patient to read  Patient Information  before starting therapy.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
• Advise patient to notify health care professional promptly if signs and symptoms of CRS (fever [≥100.4°F], feeling anxious, difficulty breathing, confusion or restlessness, chills, headache, dizziness, light-headedness, ↑ liver enzymes, fast heartbeat), neurologic problems (headache, confusion, changes in handwriting, jerking movements, trouble speaking, problems walking, rigid muscles, muscle spasms, muscle weakness in body or face, feeling restless, tremor, hearing loss, numbness, double vision, burning, throbbing, stabbing pain, tingling), liver problems (tiredness, pain in right upper abdomen, loss of appetite, dark urine, yellowing of skin or white part of eyes), or upper respiratory infections occur.
• May cause dizziness. Caution patient to avoid driving and other activities requiring alertness until response to teclistamab is known.
• Inform patients that hospitalization may be required for 48 hr after dose administration.
• Rep:   May cause fetal harm. Advise females of reproductive potential to use effective contraception and avoid breastfeeding during and for 5 mo after last dose of therapy. Assess immunoglobulin levels in newborns of mothers treated with teclistamab.
• Instruct patient to carry the  Tecvayli  Patient Wallet Card with them at all times and show it to all their health care professionals. The wallet card lists signs and symptoms of CRS and neurologic problems.

Evaluation/Desired Outcomes

Slowed progression of multiple myeloma.