glofitamab

Therapeutic Classification: antineoplastics

Pharmacologic Classification: T-cell engagers

High Alert

Relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, or large B-cell lymphoma arising from 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 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 lymphoma.

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

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

Half-Life: 7.6 days.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	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;
Geri: risk of fatal adverse reactions in older adults.

CV: edema

Derm: abdominal pain, rash

F and E: hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia

GI: ↑liver enzymes, constipation, diarrhea, nausea, vomiting

Hemat: ↓fibrinogen, anemia, lymphopenia, neutropenia, thrombocytopenia

Metab: hyperuricemia

MS: pain

Neuro: fatigue, headache, cognitive changes, confusion, delirium, disorientation, dizziness, IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME (ICANS), myelitis, peripheral neuropathy, sedation, tremor

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

Drug-drug:

May suppress activity of CYP450 drug-metabolizing enzymes (especially after the first dose on Cycle 1, Day 8; up to 14 days after the first 30 mg dose on Cycle 2, Day 1; and then during/after onset of cytokine release syndrome); careful monitoring of CYP450 substrates is recommended.

To be administered during 21-day treatment cycles.

IV (Adults ): Cycle 1, Day 1: Administer obinutuzumab 1000 mg as single dose; Cycle 1, Day 8: Administer glofitamab 2.5 mg as single dose (step-up dose 1); Cycle 1, Day 15: Administer glofitamab 10 mg as single dose (step-up dose 2); Cycle 2–12, Day 1: Administer glofitamab 30 mg as single dose. Continue glofitamab for a maximum of 12 cycles or until disease progression or unacceptable toxicity, whichever occurs first.

Solution for injection: 1 mg/mL

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 (dexamethasone 20 mg IV ≥1 hr before; acetaminophen 500 to 1000 mg PO and diphenhydramine 50 mg PO/IV or equivalent ≥30 min before) to ↓ risk and immediately evaluate patient for hospitalization at the first signs. Withhold glofitamab until CRS resolves or permanently discontinue based on severity.
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 Grade 1 ICANS occurs, continue glofitamab and monitor neurologic toxicity symptoms. If Grade 2 ICANS occurs, withhold glofitamab until neurologic toxicity symptoms improve to ≤Grade 1. If Grade 3 ICANS occurs, withhold glofitamab until neurologic toxicity symptoms improve to ≤Grade 1 for ≥7 days. If Grade 4 ICANS occurs, permanently discontinue glofitamab.
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 diphenhydramine 25 mg PO). Use oxygen therapy 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 glofitamab if severe reactions occur.
Monitor for signs and symptoms of infection, especially in patients with neutropenia (chills, cough, headache, malaise, flu-like symptoms, dysuria, hematuria, cellulitis, erythematous nonhealing wound). Dose interruption or discontinuation and supportive therapy may be necessary based on severity.
Monitor for signs and symptoms of tumor flare (lymphadenopathy, splenomegaly, fever, bone pain, rash, urinary retention) during initial therapy in patients with bulky tumors or disease located in close proximity to airways or a vital organ. Withhold glofitamab until tumor flare resolves.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
Monitor CBC with differential at baseline and regularly throughout treatment. May cause anemia, lymphopenia, thrombocytopenia, or neutropenia.
Monitor electrolytes. May cause hypokalemia, hypocalcemia, or hypophosphatemia.
Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. May ↑ liver enzymes.

Due to the risk of CRS, patients should be hospitalized during and for 24 hr after completion of infusion of step-up dose 1 (2.5 mg on Cycle 1, Day 8). Patients who experienced any grade CRS during step-up dose 1 should be hospitalized during and for 24 hr after completion of step-up dose 2 (10 mg on Cycle 1, Day 15). CRS with step-up dose 2 can occur in patients who did not experience CRS with step-up dose 1. For subsequent doses, patients who experienced ≥Grade 2 CRS with their previous infusion should be hospitalized during and for 24 hr after the completion of the next infusion. For repeat of the 2.5 mg dose, patients should be hospitalized during and for 24 hr after completion of the infusion. For repeat of the 10 mg dose, patients should be hospitalized during and for 24 hr after completion of the infusion if any grade CRS occurred during the most recent 2.5 mg dose.
Premedications in patients who experienced any Grade CRS with the previous dose: Dexamethasone 20 mg IV (if dexamethasone not available, administer prednisone 100 mg, prednisolone 100 mg, or methylprednisolone 80 mg IV) completed ≥1 hr prior to glofitamab infusion.
Premedications (cycle 1 days 8 and 15, cycle 2, cycle 3) in all patients: Dexamethasone 20 mg IV (if dexamethasone not available, administer prednisone 100 mg, prednisolone 100 mg, or methylprednisolone 80 mg IV) completed ≥1 hr prior to glofitamab infusion AND acetaminophen 500–1000 mg PO ≥30 min prior to glofitamab infusion AND antihistamine (diphenhydramine 50 mg PO/IV) completed ≥30 min prior to glofitamab infusion.
Consider
Pneumocystis jirovecii
pneumonia and cytomegalovirus infection prophylaxis in at-risk patients, and consider initiating prophylaxis against herpes virus; administer antihyperuricemics to patients at risk of tumor lysis syndrome prior to administration with glofitamab.
Prior to initiation, ensure patient is well hydrated.

IV Administration:

Explain purpose and side effects of glofitamab to patient. Do not stop receiving drug without consulting health care professional. If an appointment is missed, contact health care professional as soon as possible to reschedule. Advise patient to read Patient Information before starting therapy.
Explain need for continued medical follow-up to assess effectiveness and possible side effects of medication. Periodic lab tests and exams may be needed.
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.
Advise patient to report signs and symptoms of tumor flare, including painful or swollen lymph nodes, upper abdominal swelling, swollen spleen, fever, bone pain, rash, and difficulty urinating, to health care professional.
May cause dizziness and drowsiness. 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.
Instruct patient to notify health care professional or call 911 immediately to seek medical care if swelling of face, eyes, lips, or tongue or if difficulty swallowing or breathing occur.
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. Women of reproductive potential should be advised to use effective contraception during treatment and for 1 mo after the last dose. Advise patients not to breastfeed during glofitamab treatment and for 1 mo after the last dose.

Slowed progression of diffuse large B-cell lymphoma.

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US Brand Names ⬆