epcoritamab

EP-koe-RIT-a-mab

Therapeutic Classification: antineoplastics

Pharmacologic Classification: T-cell engagers

High Alert

Relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, including diffuse large B-cell lymphoma arising from indolent lymphoma, and high-grade B-cell lymphoma after ≥2 lines of systemic therapy.
Relapsed or refractory follicular lymphoma after ≥2 lines of systemic therapy.

Acts as a T-cell engager, binding to CD20 expressed on the surface of B cells and lymphoma cells and to the CD3 receptor on the surface of T cells, resulting in facilitated lysis of malignant cells.

Therapeutic effects:

Slowed progression of diffuse large B-cell and follicular lymphoma.

Absorption: Extent of absorption following SUBQ administration unknown.

Distribution: Well distributed to tissues.

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

Half-Life: 22 days.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
SUBQ	unknown	0.3–7 days	unknown

Contraindicated in:

Active infection;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

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

CV: bradycardia, edema, tachycardia

Derm: rash

F and E: hyperkalemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia

GI: ↑liver enzymes, abdominal pain, diarrhea, nausea, vomiting

GU: ↑serum creatinine

Hemat: anemia, leukopenia, lymphopenia, neutropenia, thrombocytopenia

Local: injection site reactions

Metab: ↓appetite

MS: pain

Neuro: fatigue, headache, aphasia, confusion, dysgraphia, IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME (ICANS), sedation, tremor

Resp: pleural effusion

Misc: cytokine release syndrome (CRS), fever, infection, tumor flare, tumor lysis syndrome

Drug-drug:

May suppress activity of CYP450 drug-metabolizing enzymes (especially after the first dose on Cycle 1, Day 1; up to 14 days after the first 48-mg dose on Cycle 1, Day 15; and then during/after onset of cytokine release syndrome); careful monitoring of CYP450 substrates is recommended.

To be administered in 28-day cycles.

Diffuse Large B-Cell Lymphoma and High-Grade B-Cell Lymphoma

SC (Adults ): Cycle 1, Day 1: 0.16 mg as single dose (step-up dose 1); Cycle 1, Day 8: 0.8 mg as single dose (step-up dose 2); Cycle 1, Day 15: 48 mg as single dose; Cycle 1, Day 22: 48 mg as single dose; Cycles 2 and 3, Days 1, 8, 15, and 22: 48 mg as single dose on each of these days; Cycles 4–9, Days 1 and 15: 48 mg as single dose on each of these days; Cycles 10 and beyond, Day 1: 48 mg as single dose on each of these days. Continue therapy until disease progression or unacceptable toxicity.

Follicular Lymphoma

SC (Adults ): Cycle 1, Day 1: 0.16 mg as single dose (step-up dose 1); Cycle 1, Day 8: 0.8 mg as single dose (step-up dose 2); Cycle 1, Day 15: 3 mg as single dose (step-up dose 3); Cycle 1, Day 22: 48 mg as single dose; Cycles 2 and 3, Days 1, 8, 15, and 22: 48 mg as single dose on each of these days; Cycles 4–9, Days 1 and 15: 48 mg as single dose on each of these days; Cycles 10 and beyond, Day 1: 48 mg as single dose on each of these days. Continue therapy until disease progression or unacceptable toxicity.

Solution for injection: 4 mg/0.8 mL; 48 mg/0.8 mL

Monitor for CRS (pyrexia, chills, hypotension, hypoxia, dyspnea, tachycardia). If Grade 1 CRS occurs with temperature ≥100.4°F, hold therapy and manage per practice guidelines. Ensure CRS symptoms are resolved before administering next dose. If Grade 2 CRS occurs with temperature ≥100.4°F, hypotension not requiring vasopressors, and/or hypoxia requiring low-flow oxygen (<6 L/min) via nasal cannula, hold therapy and manage per practice guidelines. Ensure CRS symptoms are resolved before next dose. Administer premedications before the next dose. For the next dose, monitor more frequently and consider hospitalization. If Grade 3 CRS occurs with a temperature ≥100.4°F, hypotension requiring a vasopressor (with or without vasopressin), and/or hypoxia requiring high-flow oxygen (≥6 L/min) via nasal cannula, face mask, nonrebreather mask, or Venturi mask, hold therapy and manage per practice guidelines; may need intensive care placement. Ensure CRS symptoms are resolved before the next dose. Administer premedications before the next dose. Hospitalization is required for the next dose. If Grade 3 CRS recurs, permanently discontinue epcoritamab. Manage CRS per practice guidelines and provide supportive therapy; may require intensive care. If Grade 4 CRS occurs with temperature ≥100.4°F, hypotension requiring multiple vasopressors (excluding vasopressin), and/or hypoxia requiring oxygen via positive pressure (CPAP, BiPAP, intubation, mechanical ventilation), permanently discontinue epcoritamab. Manage CRS per practice guidelines, provide supportive therapy, and possible intensive care placement.
Monitor for signs/symptoms of ICANS. Stop therapy at the first sign of neurologic toxicity, including ICANS. Rule out other causes of neurologic symptoms. If any grade of ICANS occurs, consider neurology evaluation, seizure prophylaxis with nonsedating antiseizure medication, and implement supportive care (intensive care). If Grade 1 ICANS occurs with immune effector cell-associated encephalopathy (ICE) score 7–9 or depressed level of consciousness (awakens spontaneously), hold therapy until ICANS resolves. If Grade 2 ICANS occurs with ICE score 3–6 or depressed level of consciousness (awakens to voice), hold therapy until ICANS resolves. Administer dexamethasone 10 mg IV every 6 hr (or equivalent); continue dexamethasone until resolution to Grade ≤1; then taper. If Grade 3 ICANS occurs with ICE score 0–2; depressed level of consciousness (awakens only to tactile stimulus); seizures (any clinical seizure, focal or generalized, that resolves rapidly or nonconvulsive seizures on EEG that resolve with intervention); or ↑ intracranial pressure (focal/local edema on neuroimaging), if first occurrence of Grade 3 ICANS: Hold therapy until ICANS resolves. Administer dexamethasone 10 mg IV every 6 hr (or equivalent); continue dexamethasone until resolution to Grade ≤1; then taper. If recurrent Grade 3 ICANS: Permanently discontinue therapy. Administer dexamethasone 10 mg IV every 6 hr (or equivalent); continue dexamethasone until resolution to Grade ≤1; then taper. If Grade 4 occurs with ICE score of 0; depressed level of consciousness (unarousable, requires vigorous/repetitive tactile stimuli to arouse, stupor or coma); seizures (life-threatening prolonged seizure >5 min or repetitive clinical or electrical seizures without return to baseline in between); motor findings (hemiparesis/paraparesis); or ↑ intracranial pressure/cerebral edema, with signs/symptoms of diffuse cerebral edema on neuroimaging, decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, or Cushing triad, permanently discontinue epcoritamab. Administer dexamethasone 10 mg IV every 6 hr (or equivalent); continue dexamethasone until resolution to Grade ≤1; then taper. Consider methylprednisolone 1000 mg IV daily for ≥2 days.
Assess for adverse reactions (COVID-19, pleural effusion, fatigue). If ≥Grade 3 adverse reactions occur, hold therapy until adverse reaction resolves to Grade ≤1.
Assess for infection (urinary tract infections, sepsis, COVID-19, pneumonia, upper respiratory tract infections, opportunistic infections). If Grades 1–4 infection occurs, hold therapy in patients with active infection until the infection resolves. For Grade 4, consider permanent discontinuation of epcoritamab.

Lab Test Considerations:

Verify negative pregnancy status before starting treatment.
Monitor CBC with differential. May cause neutropenia. If ANC <500/mm³, hold therapy until ANC ≥500/mm³. Consider prophylactic granulocyte colony-stimulating factor administration as appropriate.
May cause thrombocytopenia. If platelet count <50,000/mm³, hold therapy until platelet count ≥50,000/mm³.
May ↓ hemoglobin and hematocrit. If anemia occurs, hold or discontinue epcoritamab based on severity.

Ensure patient is adequately hydrated. .
Provide Pneumocystis jirovecii pneumonia prophylaxis, and consider starting prophylaxis against herpes virus to prevent herpes zoster reactivation before starting treatment.
Pre- and Postadministration Medications: Cycle 1 for all patients: Administer dexamethasone (15 mg PO or IV) or equivalent 30–120 min before each weekly dose and for 3 consecutive days following each weekly administration. Administer diphenhydramine (50 mg PO or IV) or equivalent and acetaminophen (650–1000 mg PO) 30–120 min before each weekly administration. Cycle 2 for patients who experienced Grade 2 or 3 CRS with previous dose: Administer dexamethasone (15 mg PO or IV) or equivalent 30–120 min before next administration after a Grade 2 or 3 CRS event and for 3 consecutive days following the next administration until dose is given without subsequent CRS of Grade ≥2.
Prepare and administer by a health care provider. If refrigerated, allow solution to come to room temperature for <1 hr before administration. Inspect solution visually for particulate matter and discoloration. Do not invert or vigorously shake vial during preparation processes. Use solution in the syringe immediately. If not used immediately, store the solution refrigerated for up to 24 hr or at room temperature for up to 12 hr.
Empty vial method: For 0.16 mg dose (two dilutions required): Gently swirl one 4 mg/0.8 mL vial. To perform the first dilution, label an appropriately sized empty vial as “Dilution A” and transfer 0.8 mL (4 mg) of epcoritamab into the Dilution A vial; then add 4.2 mL of 0.9% NaCl to the Dilution A vial, resulting in an initially diluted solution of epcoritamab 0.8 mg/mL. Gently swirl the Dilution A vial for 30–45 sec. To perform the second dilution, label an appropriately sized empty vial as “Dilution B” and transfer 2 mL (epcoritamab 1.6 mg) of solution from the Dilution A vial into the Dilution B vial (the Dilution A vial is no longer needed). Add 8 mL of 0.9% NaCl to the Dilution B vial, resulting in a final epcoritamab concentration of 0.16 mg/mL. Gently swirl the Dilution B vial for 30–45 sec. Withdraw 1 mL (0.16 mg) of epcoritamab from the Dilution B vial into a syringe and label as epcoritamab 0.16 mg/1 mL.
- For 0.8 mg dose (one dilution required): Gently swirl one 4 mg/0.8 mL vial. To perform the dilution, label an appropriately sized empty vial as “Dilution A” and transfer 0.8 mL (4 mg) of epcoritamab into the Dilution A vial; then add 4.2 mL of 0.9% NaCl to the Dilution A vial, resulting in a final diluted solution of epcoritamab 0.8 mg/mL. Gently swirl the Dilution A vial for 30–45 sec. Withdraw 1 mL (0.8 mg) of epcoritamab from the Dilution A vial into a syringe and label as epcoritamab 0.8 mg/1 mL.
Syringe method: For 0.16 mg dose (two dilutions required): Gently swirl one 4 mg/0.8 mL vial. To perform the first dilution, label an appropriately sized syringe as “Dilution A.” Withdraw 4.2 mL of 0.9% NaCl into the Dilution A syringe; include 0.2 mL of air in the syringe. In a new syringe (labeled as “Syringe 1”), withdraw 0.8 mL (4 mg) of epcoritamab. Connect the two syringes and push the 0.8 mL (4 mg) of epcoritamab into the Dilution A syringe. This initial diluted solution contains 0.8 mg/mL of epcoritamab. Mix gently by inverting the connected syringes 180 degrees five times. Disconnect the syringes and discard Syringe 1. To perform the second dilution, label an appropriately sized syringe as “Dilution B.” Withdraw 8 mL of 0.9% NaCl into the Dilution B syringe; include 0.2 mL of air in the syringe. Label another appropriately sized syringe as “Syringe 2.” Connect Syringe 2 to the Dilution A syringe and transfer 2 mL (epcoritamab 1.6 mg) of solution into Syringe 2 (the Dilution A syringe is no longer needed). Connect Syringe 2 to the Dilution B syringe and push the 2 mL of solution from Syringe 2 into the Dilution B syringe, resulting in a final epcoritamab concentration of 0.16 mg/mL. Mix gently by inverting the connected syringes 180 degrees five times. Withdraw 1 mL (0.16 mg) of diluted epcoritamab from the Dilution B syringe into a new syringe (the Dilution B syringe is no longer needed) and label the syringe with the dose strength of epcoritamab 0.16 mg/1 mL.
- For 0.8 mg dose (one dilution required): Gently swirl one 4 mg/0.8 mL vial. To perform the dilution, label an appropriately sized syringe as “Dilution A.” Withdraw 4.2 mL of 0.9% NaCl into the Dilution A syringe; include 0.2 mL of air in the syringe. In a new syringe (labeled as “Syringe 1”), withdraw 0.8 mL (4 mg) of epcoritamab. Connect the two syringes and push the 0.8 mL (4 mg) of epcoritamab into the Dilution A syringe. This initial diluted solution contains 0.8 mg/mL of epcoritamab. Mix gently by inverting the connected syringes 180 degrees five times. Disconnect the syringes and discard Syringe 1. Connect a new syringe to the Dilution A syringe and transfer 1 mL (0.8 mg) of epcoritamab from the Dilution A syringe into the new syringe (the Dilution A syringe is no longer needed) and label the syringe with the dose strength of epcoritamab 0.8 mg/1 mL.
- For 3 mg dose (no dilution required): Gently swirl one 4 mg/0.8 mL vial. Withdraw 0.6 mL (3 mg) of epcoritamab from the vial into a syringe and label as epcoritamab 3 mg/0.6 mL.
- For 48 mg dose (no dilution required): Gently swirl one 48 mg/0.8 mL vial. Withdraw 0.8 mL (48 mg) of epcoritamab from the vial into a syringe and label as epcoritamab 48 mg/0.8 mL.
SC: Inject required dose volume into the tissue of the lower part of the abdomen (preferred site) or the thigh. Rotate injection site from left to right (or vice versa), particularly during the weekly administrations (in Cycles 1–3). Do not inject into tattoos; scars; or areas where the skin is red, bruised, tender, hard, or not intact.
Recommendations for Restarting Therapy After Dosage Delay: Diffuse Large B-Cell Lymphoma and High-Grade B-Cell Lymphoma: Last dose 0.16 mg (e.g., on Cycle 1, Day 1), if >8 days, repeat Cycle 1 schedule starting at step-up dose 1 (0.16 mg). Following the repeat of Cycle 1 schedule, resume the planned treatment schedule. Last dose 0.8 mg (e.g., on Cycle 1, Day 8), if <14 days, administer 48 mg; then resume the planned treatment schedule. If >14 days, repeat Cycle 1 schedule starting at step-up dose 1 (0.16 mg). Following the repeat of Cycle 1 schedule, resume the planned treatment schedule. Last dose 48 mg (e.g., on Cycle 1, Day 15 onward), if <6 wk, administer 48 mg; then resume the planned treatment schedule. If >6 wk, repeat Cycle 1 schedule starting at step-up dose 1 (0.16 mg). Following the repeat of Cycle 1 schedule, resume the planned treatment schedule.
Recommendations for Restarting Therapy After Dosage Delay: Follicular Lymphoma: Last dose 0.16 mg (e.g., on Cycle 1, Day 1), if >8 days, repeat Cycle 1 schedule starting at step-up dose 1 (0.16 mg). Following the repeat of Cycle 1 schedule, resume the planned treatment schedule. Last dose 0.8 mg (e.g., on Cycle 1, Day 8), if >8 days, repeat Cycle 1 schedule starting at step-up dose 1 (0.16 mg). Following the repeat of Cycle 1 schedule, resume the planned treatment schedule. Last dose 3 mg (e.g., on Cycle 1, Day 15)if <14 days, administer 48 mg; then resume the planned treatment schedule. If >14 days, repeat Cycle 1 schedule starting at step-up dose 1 (0.16 mg). Following the repeat of Cycle 1 schedule, resume the planned treatment schedule. Last dose 48 mg (e.g., on Cycle 1, Day 22 onward), if <6 wk, administer 48 mg; then resume the planned treatment schedule. If >6 wk, repeat Cycle 1 schedule starting at step-up dose 1 (0.16 mg). Following the repeat of Cycle 1 schedule, resume the planned treatment schedule.

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.
Inform patient of the risk of CRS and to immediately contact health care professional of any signs and symptoms of fever, hypotension, hypoxia, chills, tachycardia, headache, or dyspnea. Advise patients with diffuse large B-cell lymphoma or high-grade B-cell lymphoma that they should be hospitalized for 24 hr after administration of the Cycle 1, Day 15, dosage of 48 mg.
Advise patient of the risk of ICANS; to immediately contact health care professional if signs and symptoms of confusion, lethargy, tremor, dysgraphia, aphasia, or nonconvulsive status epilepticus occur; and that the onset of events may be delayed.
Advise patients who experience symptoms of CRS or ICANS not to drive and refrain from operating heavy or potentially dangerous machinery until events resolve.
Advise patient of the risk of serious infections and to contact their health care professional for signs or symptoms of serious infection.
Educate patient on the signs and symptoms associated with cytopenias, including neutropenia and febrile neutropenia, anemia, and thrombocytopenia.
Rep: May cause fetal harm. Advise women of reproductive potential to inform their health care professional if pregnancy is suspected or planned or if breastfeeding. Advise patient not to breastfeed during treatment and for 4 mo after last dose. Advise patient who could become pregnant to use effective contraception during therapy and for 4 mo after the last dose.

Slowed progression of diffuse large B-cell and follicular lymphoma.

Epkinly

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