talquetamab

tal-KWE-ta-mab

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies, T-cell engagers

High Alert

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

Acts as a T-cell engager, binding to the CD3 receptor expressed on the surface of T-cells and G protein-coupled receptor class C group 5 member D expressed on the surface of multiple myeloma cells, resulting in facilitated lysis of malignant cells.

Therapeutic effects:

Slowed progression of multiple myeloma.

Absorption: 59% absorbed following SUBQ administration.

Distribution: Well distributed to tissues.

Metabolism/Excretion: Metabolized into small peptides by catabolic pathways. Excretion pathway unknown.

Half-Life: 8–12 days.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
SUBQ	unknown	2–3 days	unknown

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

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

CV: edema, hypotension, tachycardia

Derm: dry skin, erythema, nail disorder, pruritus, rash

F and E: hyponatremia, hypophosphatemia

GI: ↑liver enzymes, constipation, diarrhea, dry mouth, dysphagia, hepatotoxicity, hypoalbuminemia, nausea, stomatitis

Hemat: anemia, leukopenia, lymphopenia, neutropenia, thrombocytopenia

Local: injection site reactions

Metab: ↓appetite, weight loss

MS: pain

Neuro: ageusia, dysgeusia, encephalopathy, fatigue, headache, motor dysfunction, neuropathy, IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME (ICANS)

Resp: cough, dyspnea, hypoxia

Misc: chills, cytokine release syndrome (CRS), fever, infection

Drug-drug:

May suppress activity of CYP450 drug-metabolizing enzymes (especially after first dose on Day 1 and up to 14 days after the first treatment dose and during/after onset of cytokine release syndrome); careful monitoring of CYP450 substrates is recommended.

Weekly Dosing Schedule

SC (Adults ): Day 1 (step-up dose 1): 0.01 mg/kg as single dose; Day 4 (step-up dose 2): 0.06 mg/kg as single dose; Day 7 (1st treatment dose): 0.4 mg/kg as single dose; Weekly dosing schedule: 0.4 mg/kg administered 1 wk after first treatment dose and then once weekly; continue until disease progression or unacceptable toxicity.

Biweekly Dosing Schedule

SC (Adults ): Day 1 (step-up dose 1): 0.01 mg/kg as single dose; Day 4 (step-up dose 2): 0.06 mg/kg as single dose; Day 7 (step-up dose 3): 0.4 mg/kg as single dose; Day 10 (1st treatment dose): 0.8 mg/kg as single dose; Biweekly dosing schedule: 0.8 mg/kg administered 2 wk after first treatment dose and then every 2 wk; continue until disease progression or unacceptable toxicity.

Solution for SUBQ injection: 2 mg/mL; 40 mg/mL

Monitor for skin reactions, including rash, papules, and erythema; dose interruption may be necessary based on severity. If Grade 3 or 4 skin reactions occur, hold talquetamab until improves to Grade ≤1. Refer to Restarting Therapy After Weekly or Biweekly Dosage Delays section below.
Monitor for CRS (fever, rigors, tachycardia, hypotension, confusion, delirium, arthralgia, myalgia, headache, dizziness, nausea, vomiting, shortness of breath, wheezing); administer pretreatment medications to ↓ risk and immediately evaluate patient for hospitalization at the first signs. Due to the risk of CRS, patients should be hospitalized for 48 hr after administration of all doses within the step-up dosing schedule. If Grade 1 CRS (temperature >100.4° F occurs), hold talquetamab until CRS resolves. Refer to Restarting Therapy After Weekly or Biweekly Dosage Delays sections below. Administer premedications prior to next dose. If Grade 2 CRS (temperature >100.4° F with hypotension responsive to fluids and not requiring vasopressors or oxygen requirement of low-flow nasal cannula [< 6 L/min]) occurs, hold talquetamab until CRS resolves. Refer to Restarting Therapy After Weekly or Biweekly Dosage Delays sections below; patients should be hospitalized for 48 hr following the next dose. Administer premedications prior to next dose. If Grade 3 CRS (temperature >100.4°F with hypotension requiring one vasopressor [with or without vasopressin] or oxygen requirement of high-flow oxygen [> 6 L/min] via nasal cannula, face mask, nonrebreather mask, or Venturi mask) occurs, for a duration <48 hr, hold talquetamab therapy until CRS resolves. Provide supportive therapy, which may include intensive care. Refer to Restarting Therapy After Weekly or Biweekly Dosage Delays sections below; patients should be hospitalized for 48 hr following the next dose. Administer premedications prior to next dose. For recurrent or duration of ≥48 hr, permanently discontinue talquetamab and provide supportive therapy, which may include intensive care. If Grade 4 CRS (temperature >100.4° F with hypotension requiring multiple vasopressors [excluding vasopressin] or oxygen requirement of positive pressure [e.g., continuous positive airway pressure, bilevel positive airway pressure, intubation, mechanical ventilation]) occurs, permanently discontinue talquetamab and provide supportive therapy, which may include intensive care.
Monitor for signs and symptoms of ICANS (confusion, altered consciousness, anxiety, delirium, dizziness, weakness, seizures, tremor, myoclonus, asterixis, aphasia, lethargy, difficulty concentrating, agitation, hallucinations). Patients should be hospitalized for 48 hr after administration of all doses within the step-up dosing schedule. If Grade 1 ICANS (ICE score 7–9 or depressed level of consciousness awakening spontaneously) occurs, hold talquetamab until resolution. Refer to Restarting Therapy After Weekly or Biweekly Dosage Delays sections below. Consider nonsedating antiseizure medications (e.g., levetiracetam). If Grade 2 ICANS (ICE score 3–6 or depressed level of consciousness awakening to voice) occurs, hold talquetamab. Administer dexamethasone 10 mg IV every 6 hr until resolution to Grade ≤1; then taper. Consider nonsedating antiseizure medications. Refer to Restarting Therapy After Weekly or Biweekly Dosage Delays sections below. If Grade 3 ICANS (ICE score 0–2, depressed level of consciousness awakening only to tactile stimulus, seizures, raised intracranial pressure, or focal edema) occurs: First occurrence: Hold talquetamab. Administer dexamethasone 10 mg IV every 6 hr until resolution to Grade ≤1; then taper. Consider nonsedating antiseizure medications. Refer to Restarting Therapy After Weekly or Biweekly Dosage Delays sections below; hospitalize for 48 hr postdose. Recurrent: Permanently discontinue talquetamab. Administer dexamethasone 10 mg IV every 6 hr until resolution to Grade ≤1; then taper. Consider nonsedating antiseizure medications. If Grade 4 ICANS (ICE score 0, unarousable or requires vigorous stimuli, prolonged or repetitive seizures, motor findings, or raised intracranial edema/cerebral edema) occurs, permanently discontinue talquetamab. Administer dexamethasone 10 mg IV every 6 hr or methylprednisolone 1000 mg/day IV for ≥2 days until resolution to Grade ≤1; then taper. Consider nonsedating antiseizure medications.
Monitor for signs of anaphylaxis (urticaria, dyspnea, wheezing) and angioedema (facial or throat swelling, hoarseness) following injection. Provide necessary emergency care. Medications (antihistamines, corticosteroids, epinephrine) and equipment should be readily available in the event of a severe reaction. If anaphylaxis or other severe allergic reaction occurs, discontinue talquetamab immediately.
Assess for signs of infection (fever; dyspnea; sweats; chills; muscle aches; cough; blood in phlegm; weight loss; frequent or painful urination; warm, red, or painful skin or sores; diarrhea; abdominal pain), including tuberculosis, prior to and periodically during therapy. New infections should be monitored closely; most common are upper respiratory tract infections, sinusitis, bronchitis, and urinary tract infections. For all grades of infection, hold talquetamab in the step-up phase until infection resolves. If Grade 3 infection occurs, hold talquetamab during the treatment phase until infection improves to Grade ≤1 within 28 days. If treatment is withheld for >28 days, restart step-up dosing when infection improves to Grade ≤1. If Grade 4 infection occurs, consider permanent discontinuation of talquetamab; if not permanently discontinued, hold subsequent treatment doses (i.e., doses administered after step-up dosing schedule) until adverse reaction improves to Grade ≤1. If treatment is held for >28 days, restart step-up dosing when infection improves to Grade ≤1.
Monitor for signs and symptoms of hepatotoxicity (fatigue, nausea, upper abdominal pain, jaundice, scleral icterus, dark urine, clay-colored stools).
Obtain weight at baseline and monitor regularly for weight loss. If Grade 1–2 weight loss occurs, provide supportive care; consider holding talquetamab if not responsive to supportive care. Refer to Restarting Therapy After Weekly or Biweekly Dosage Delays sections below. If Grade 3 weight loss occurs, hold talquetamab until resolution to Grade ≤1 and provide supportive care. Refer to Restarting Therapy After Weekly or Biweekly Dosage Delays sections below. If Grade 4 weight loss occurs, permanently discontinue talquetamab.
Monitor for oral toxicities, including dysgeusia, ageusia, xerostomia, dysphagia, and stomatitis. Dose interruption or discontinuation may be necessary based on severity. Opioid analgesics may be necessary for pain control. If Grade 1–2 oral toxicities occur, provide supportive care; consider holding talquetamab if not responsive to supportive care. Refer to Restarting Therapy After Weekly or Biweekly Dosage Delays sections below. If Grade 3 oral toxicities occur, hold talquetamab until resolution to Grade ≤1 and provide supportive care. Refer to Restarting Therapy After Weekly or Biweekly Dosage Delays sections below. If Grade 4 oral toxicities occur, permanently discontinue talquetamab.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
Obtain CBC with differential at baseline and during treatment as clinically indicated. May cause anemia, neutropenia, leukopenia, lymphocytopenia, and thrombocytopenia. If ANC <0.5 × 10⁹/L, hold talquetamab until ANC ≥0.5 × 10⁹/L. If febrile, hold talquetamab until ANC ≥1 × 10⁹/L and fever resolves. If platelet count <25,000/mcL or platelet count 25,000–50,000/mcL with bleeding, hold talquetamab until platelet count ≥25,000/mcL and no evidence of bleeding. If Hgb <8 g/dL, hold talquetamab until Hgb ≥8 g/dL. Refer to Restarting Therapy After Weekly or Biweekly Dosage Delays sections below.
Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. May ↑ liver enzymes.
May cause hyponatremia and hypophosphatemia.

Only administer by a qualified health care professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity, including ICANS.
For pretreatment, administer corticosteroid (dexamethasone 16 mg oral/IV or equivalent), antihistamine (diphenhydramine 50 mg oral/IV or equivalent), and antipyretic (acetaminophen 650–1000 mg oral/IV or equivalent) 1–3 hr prior to each dose of talquetamab in the step-up dosing schedule and prior to restarting talquetamab following dosage delays. Administration of pretreatment medications may be required for subsequent doses in patients who repeat doses within the step-up schedule due to dose delays or for those who experienced CRS.
SC: Administer via SUBQ injection into the SUBQ tissue of the abdomen (preferred injection site). Alternatively, may be injected into the SUBQ tissue at other sites (e.g., thigh). If multiple injections are required, injections should be ≥2 cm apart. Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard, or not intact.
- Use patient's actual body weight to determine step-up and treatment doses. Do not dilute prior to administration. Do not combine vials of different concentrations to achieve treatment dose. Solution is colorless to light yellow; do not use if the solution is discolored, cloudy, or contains foreign particles. Allow vial to adjust to room temperature for about 15 min. Gently swirl for approximately 10 sec to mix; do not shake. Withdraw the required injection volume from the vial(s) into an appropriately sized syringe using a transfer needle. Each injection volume should not exceed 2 mL; divide doses requiring >2 mL equally into multiple polypropylene or polycarbonate syringes with stainless steel injection needles. The prepared syringes should be administered immediately. If immediate administration is not possible, store the solution refrigerated for up to 24 hr followed by at room temperature for up to 24 hr. Discard if stored for >24 hr.
Restarting Therapy After Weekly Dosage Delays: Last dose = 0.01 mg/kg: If >7 days, restart at step-up dose 1 (0.01 mg/kg). If >28 days due to adverse reaction, evaluate benefit-risk before restarting. Last dose = 0.06 mg/kg: If 8–28 days, repeat step-up dose 2 (0.06 mg/kg) and continue schedule. If >28 days, restart at step-up dose 1 (0.01 mg/kg). Last dose = 0.4 mg/kg: If 8–28 days, continue at 0.4 mg/kg weekly. If 29–56 days, restart at step-up dose 2 (0.06 mg/kg). If >56 days, consider permanent discontinuation or restart at step-up dose 1 (0.01 mg/kg).
Restarting Therapy After Biweekly Dosage Delays: Last dose = 0.01 mg/kg: If >7 days, restart at step-up dose 1 (0.01 mg/kg). If >28 days due to adverse reaction, evaluate benefit-risk before restarting. Last dose = 0.06 mg/kg: If 8–28 days, repeat step-up dose 2 (0.06 mg/kg) and continue schedule. If >28 days, restart at step-up dose 1 (0.01 mg/kg). Last dose = 0.4 mg/kg: If 8–28 days, continue at 0.4 mg/kg weekly. If 29–56 days, restart at step-up dose 2 (0.06 mg/kg). If >56 days, consider permanent discontinuation or restart at step-up dose 1 (0.01 mg/kg). Last dose = 0.8 mg/kg: If 15–28 days, continue at 0.8 mg/kg every 2 wk. If 29–56 days, restart at step-up dose 3 (0.4 mg/kg). If >56 days, consider permanent discontinuation or restart at step-up dose 1 (0.01 mg/kg).

Explain purpose and side effects of talquetamab. If an appointment is missed, contact health care professional as soon as possible to reschedule. Advise patient to read Patient Information before starting and periodically during therapy in case of changes.
Explain need for continued medical follow-up to assess effectiveness and possible side effects of medication. Periodic lab tests will be needed.
Advise patient to notify health care professional if signs and symptoms of infusion-related reactions (shortness of breath, cough, chills, nausea) occur within 24 hr of start of infusion.
Inform patient to seek treatment for signs and symptoms of neurologic toxicity (difficulty waking, confusion, anxiety, agitation, dizziness, weakness, seizures, shaking, stiffness, difficulty concentrating or speaking, hallucinations) or CRS (fever, chills, fast HR, low BP, joint aches, muscle aches, headache, dizziness, nausea, vomiting, trouble breathing).
Instruct patient to notify health care professional promptly if signs and symptoms of infection (fever, sore throat, cough, sinus pain, lower back or side pain, difficult or painful urination) occur. Caution patient to avoid crowds and persons with known infections.
Instruct patient to inspect oral mucosa for dryness, redness, and ulceration. If mouth sores occur, advise patient to use sponge brush and rinse mouth with water after eating and drinking. Consult health care professional if pain interferes with eating. Stomatitis pain treatment may require opioid analgesics.
Inform the patient to report signs or symptoms of liver toxicity (tiredness, nausea, upper abdominal pain, yellowing of skin or eyes, dark urine, light-colored stools).
Advise patient to report skin rash, extreme itchiness, or weight loss.
May cause dizziness and drowsiness. Caution patient to avoid driving or other activities requiring alertness during and for 48 hr after step-up dosing and with new onset of any neurologic toxicity.
Advise patient to stay hydrated; side effects can include diarrhea, nausea, and vomiting.
Advise patient to avoid live vaccines during 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.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during treatment and for 3 mo after last dose. Advise patient to notify health care professional if pregnancy is suspected or planned and to avoid breastfeeding during therapy.

Slowed progression of multiple myeloma.

Talvey

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