elranatamab

EL-ra-NAT-a-mab

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies, T-cell engagers

High Alert

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.

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 effects:

Slowed progression of multiple myeloma.

Absorption: 56% absorbed following SUBQ administration.

Distribution: Not widely distributed to tissues.

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

Half-Life: 22 days.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
SUBQ	unknown	7 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: arrhythmia, edema, HF

Derm: dry skin, rash, skin exfoliation

F and E: hypokalemia

GI: ↑liver enzymes, constipation, diarrhea, hepatotoxicity, hypoalbuminemia, nausea, vomiting, abdominal pain

GU: ↑serum creatinine, acute kidney injury

Hemat: anemia, bleeding, leukopenia, lymphopenia, neutropenia, thrombocytopenia, thrombosis

Local: injection site reactions

Metab: ↓appetite

MS: pain

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

Resp: cough, dyspnea

Misc: cytokine release syndrome (CRS), fever, hypogammaglobulinemia, 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 32 mg dose on Day 4 and during/after onset of cytokine release syndrome); careful monitoring of CYP450 substrates is recommended.

SC (Adults ): Day 1 (step-up dose 1): 12 mg as single dose; Day 4 (step-up dose 2): 32 mg as single dose; Day 8 (1st treatment dose): 76 mg as single dose; Weekly dosing schedule: 76 mg administered 1 wk after first treatment dose and then once weekly through Wk 24; Biweekly dosing schedule (for responders only): 76 mg on Wk 25; then every 2 wk thereafter.

Solution for SUBQ injection: 40 mg/mL

Monitor for signs and symptoms of injection site reactions and hypersensitivity reactions (fever, chills, sweating, myalgia, headache, dizziness, nausea, vomiting, urticaria, pruritus, shortness of breath, wheezing ) during treatment and the following 24 hr. Begin symptomatic therapy (acetaminophen 650 mg PO, dexamethasone 20 mg PO/IV, and diphenhydamine 25 mg PO). Oxygen therapy should be utilized for respiratory distress with hypoxemia. Manage mild hypotension with IV fluids. Severe nausea and vomiting may respond to a combination of agents from different drug classes. Discontinue therapy for severe reactions.
Monitor level of consciousness and neurologic checks regularly for signs and symptoms of neurologic toxicities (headache, tremors, motor weakness, seizures, confusion, delirium, aphasia). Institute seizure precautions. If ICANS develops during treatment, withhold until symptoms resolve. If ICANS Grade 1, continue elranatamab and monitor neurologic toxicity symptoms. If ICANS Grade 2, give dexamethasone; continue until resolution to ≤Grade 1; then taper; monitor closely for 48 hr. If ICANS Grade 3, give dexamethasone; continue until resolution to ≤Grade 1; then taper; hospitalize for 48 hr. If ICANS Grade 4 or recurrent Grade 3, give dexamethasone; continue until resolution to ≤Grade 1; then taper; hospitalize patient. Consider nonsedating antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis.
Monitor for signs and symptoms of CRS (fever, rigors, tachycardia, hypotension, confusion, delirium, arthralgia, myalgia, headache, dizziness, nausea, vomiting, shortness of breath, wheezing). Administer pretreatment medications (acetaminophen 650 mg PO, dexamethasone 20 mg PO/IV, and diphenhydamine 25 mg PO) ≥30 min before to ↓ risk, and immediately evaluate patient for hospitalization at the first signs. Use current practice guidelines to manage CRS and provide supportive therapy, which may include intensive care and temporary discontinuation of therapy based on severity.
Monitor for signs and symptoms of infection, especially in patients with neutropenia (fever, chills, cough, headache, malaise, flu-like symptoms, dysuria, hematuria, cellulitis, erythematous nonhealing wound). Monitoring and administer appropriate antimicrobials and antiviral medications for identified infections. If fever develops during the neutropenic phase (ANC ≤500 cells/mm³), obtain cultures and start empiric antibiotics. Consider prophylactic antibiotic therapy with a fluoroquinolone in high-risk patients with expected prolonged (>7 days) neutropenia (ANC ≤100 cells/mm³). Dose interruption or discontinuation may be necessary based on severity.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
Monitor CBC with differential at baseline and regularly throughout treatment. Administer colony stimulating factors (filgrastim or sargramostim) in patients that appear to be at risk for severe neutropenia.
- Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated.

REMS: Should only be administered by a qualified and trained health care professional with appropriate medical support to manage severe reactions such as CRS and ICANS.
Due to the risk of CRS, patients should be hospitalized for 48 hr after administration of the first step-up dose and for 24 hr after administration of the second step-up dose.
Pretreatment: Administer acetaminophen 650 mg PO, dexamethasone 20 mg PO/IV, and diphenhydamine 25 mg PO 1 hr before the 1st three doses of elranatamab in the step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose. Administration of pretreatment medications may be required for subsequent doses in patients who resume therapy following a dosage delay.
Restarting Therapy after a Dosage Delay on Step 1 (12 mg): If <2 wk since last dose, restart elranatamab at step-up dose 2 (32 mg) and administer premedications prior to the dose. If tolerated, ↑ dose to 76 mg 4 days later. If >2 wk since last dose, restart elranatamab step-up dosing schedule at step-up dose 1 (12 mg) and administer premedications prior to the dose.
- Restarting Therapy after a Dosage Delay on Step 2 (32 mg)If <2 wk since last dose, restart elranatamab at 76 mg and administer premedications prior to the dose. If >2 wk and <4 wk since last dose, restart at step-up dose 2 (32 mg) and administer premedications prior to the dose. If tolerated, ↑ dose to 76 mg 1 wk later. If >4 wk since last dose, restart elranatamab step-up dosing schedule at step-up dose 1 (12 mg) and administer premedications prior to the dose
- Restarting Therapy after a Dosage Delay on 76 mgIf <6 wk since last dose, restart elranatamab at 76 mg and administer premedications prior to the dose. If >6 wk and <12 wk since last dose, restart at step-up dose 2 (32 mg) and administer premedications prior to the dose. If tolerated, ↑ dose to 76 mg 1 wk later. If > 12 wk since last dose, restart elranatamab step-up dosing schedule at step-up dose 1 (12 mg) and administer premedications prior to the dose. Consider benefit-risk of restarting treatment in patients who require a dose delay of >42 days due to an adverse reaction.
SC: Inject required dose volume into the SUBQ tissue of the abdomen (preferred injection site); alternatively, may inject into SUBQ tissue at other sites (e.g., thigh). Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard, or not intact. Solution is clear to slightly opalescent and colorless to pale brown; do not administer if solution is discolored or contains particulate matter. Remove the appropriate strength vial from refrigerated storage; then bring to room temperature; do not warm in any other way. Withdraw the required injection volume from the vial into an appropriately sized syringe with stainless steel injection needles (30 G or wider) and polypropylene or polycarbonate syringe material. Do not dilute. Discard unused portion. If prepared syringes are not used immediately, refrigerate for a maximum of 4 hr.

Explain the purpose and side effects of elranatamab to patient. If an appointment is missed, contact health care professional as soon as possible to reschedule. Advise patient to read Medication Guide before starting and periodically during therapy in case of changes.
REMS: Explain need for continued medical follow-up to assess effectiveness and possible side effects of medication. Teach the patient how to recognize and respond to signs and symptoms of neurologic toxicities, including CRS and ICANS. Advise patient to wear medical ID describing disease process and medication regimen at all times in case of emergencies. Explain and assist completion of the patient wallet card, which should be carried by the patient at all times. More information be found at ELREXFIO REMS (https://www.elrexfiorems.com).
Instruct patient to notify health care professional or call 911 immediately to seek medical care if any signs of neurologic toxicity (headache, tremors and shaking, body weakness, seizures, confusion, delirium, difficulty with speech or writing) or CRS (fever; shaking chills; fast heartbeat; low blood pressure; confusion; muscle or joint pains; headache; dizziness; nausea; vomiting; trouble breathing; wheezing; swelling of face, eyes, lips, or tongue; difficulty swallowing/breathing) occur.
Advise patient to avoid driving or operating heavy or potentially dangerous machinery during and for 48 hr after step-up dosing and with new onset of any neurologic toxicity. Otherwise, caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to notify health care professional if signs and symptoms of infusion reactions (fever, chills or shivering, muscle or joint pain, nausea, vomiting, diarrhea, tiredness, dizziness, sweating, hives, itching, shortness of breath, wheezing) occur.
Advise patient to report symptoms of infection and neutropenia (fever, chills, cough, headache, fatigue, weakness, flu-like symptoms, painful or bloody urination, rash, nonhealing wound).
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 patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Advise patients who may become pregnant to use effective contraception during treatment and for ≥4 mo following the last dose. Elranatamab is associated with hypogammaglobulinemia; therefore, assessment of immunoglobulin levels in newborns of mothers treated with elranatamab should be considered. Advise women not to breastfeed during treatment with elranatamab and for 4 mo after the last dose.

Slowed progression of multiple myeloma.

Elrexfio

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