Version May 2024
Cytokine release syndrome, which may be serious or life-threatening, occurred in patients receiving tebentafusp. Monitor for at least 16 hours following first 3 infusions and then as clinically indicated.
Note: Ensure patients are euvolemic prior to initiating tebentafusp infusion. Administer the first 3 tebentafusp infusions in an appropriate health care setting with immediate access to medications and resuscitative equipment to manage cytokine release syndrome. If no ≥ grade 2 hypotension (requiring medical intervention) during or after the third infusion, may administer subsequent doses in an ambulatory care setting.
Uveal melanoma, unresectable or metastatic, HLA- A*02:01-positive (Ref):
Day 1: IV: 20 mcg.
Day 8: IV: 30 mcg.
Day 15: IV: 68 mcg.
Day 22 and beyond: IV: 68 mcg once weekly until disease progression or unacceptable toxicity.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl 30 to 89 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in tebentafusp pharmacokinetics were observed in mild to moderate kidney impairment.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatic impairment prior to treatment initiation:
Mild (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to 1.5 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in tebentafusp pharmacokinetics were observed in mild hepatic impairment.
Moderate (total bilirubin >1.5 to 3 times ULN and any AST) or severe (total bilirubin >3 to 10 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatotoxicity during treatment:
Grade 3 or 4 ALT or AST elevations: Withhold tebentafusp until ≤ grade 1 (or baseline). Resume tebentafusp at same dose level if the elevated liver enzymes occur in the setting of grade 3 cytokine release syndrome (CRS); resume dose escalation if next administration is tolerated. If the elevated liver enzymes occur outside the setting of grade 3 CRS, resume dose escalation if the current tebentafusp dose is <68 mcg (or resume at the same dose level if dose escalation has completed). Administer IV corticosteroids if no improvement within 24 hours.
Note: No tebentafusp dose reduction is recommended. See table for tebentafusp dose modifications for adverse reactions.
|
Adverse reaction |
Severity |
Tebentafusp dose modification |
|---|---|---|
|
Cytokine release syndrome (CRS) |
Moderate (temperature ≥38°C with hypotension that responds to fluids [does not require vasopressors] or hypoxia requiring low flow nasal canula [≤6 L/minute] or blow-by oxygen) |
If hypotension and hypoxia do not improve within 3 hours or CRS worsens, escalate treatment and manage according to the next higher severity level. For moderate CRS that is persistent (lasting 2 to 3 hours) or recurrent, administer corticosteroid premedication (eg, dexamethasone 4 mg or equivalent) at least 30 minutes prior to the next dose. |
|
Severe (temperature ≥38°C with hemodynamic instability requiring a vasopressor [with or without vasopressin] or worsening hypoxia or respiratory distress requiring high flow nasal canula [>6 L/minute oxygen] or face mask) |
Withhold tebentafusp until CRS and sequelae have resolved. Administer IV corticosteroid (eg, methylprednisolone 2 mg/kg/day or equivalent). Resume tebentafusp at the same dose level (do not escalate dose if severe CRS occurred during initial dose escalation; resume escalation once dose is tolerated). For severe CRS, administer corticosteroid premedication (eg, dexamethasone 4 mg or equivalent) at least 30 minutes prior to the next dose. | |
|
Life-threatening (temperature ≥38°C) with: Hemodynamic instability requiring multiple vasopressors (excluding vasopressin) Worsening hypoxia or respiratory distress despite oxygen administration requiring positive pressure |
Permanently discontinue tebentafusp. Administer IV corticosteroid (eg, methylprednisolone 2 mg/kg/day or equivalent). | |
|
Skin reactions |
If skin reactions occur, treat with antihistamines and topical or systemic steroids (depending on severity and persistence of symptoms). | |
|
Grade 2 or 3 |
Withhold tebentafusp until ≤ grade 1 (or baseline), then resume at the same dose level (do not escalate dose if grade 3 skin reactions occurred during initial dose escalation; resume escalation once dose is tolerated). For persistent reactions not responding to oral steroids, consider IV corticosteroid (eg, methylprednisolone 2 mg/kg/day or equivalent). | |
|
Grade 4 |
Permanently discontinue tebentafusp. Administer IV corticosteroid (eg, methylprednisolone 2 mg/kg/day or equivalent). | |
|
Other adverse reaction |
Grade 3 |
Withhold tebentafusp until ≤ grade 1 (or baseline), then resume at the same dose level (do not escalate dose if other grade 3 adverse reaction occurred during initial dose escalation; resume escalation once dose is tolerated). |
|
Grade 4 |
Permanently discontinue tebentafusp. | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Edema (45%), flushing (<20%), hypertension (<20%), hypotension (39%; severe hypotension: 2%), sinus tachycardia (<20%), tachycardia (<20%)
Dermatologic: Alopecia (<20%), erythema of skin (24% to 25%), hair discoloration (20%), hypopigmentation (28%), night sweats (<20%), pruritus (69%), skin hyperpigmentation (<20%), skin rash (83%), xeroderma (31%)
Endocrine & metabolic: Decreased serum albumin (47%), decreased serum calcium (45%), decreased serum glucose (18%), decreased serum magnesium (34%), decreased serum phosphate (51%), decreased serum potassium (17%), decreased serum sodium (30%), increased amylase (23%), increased serum calcium (13%), increased serum glucose (66%), increased serum potassium (29%)
Gastrointestinal: Abdominal pain (45%), constipation (<20%), decreased appetite (<20%), diarrhea (25%; grades 3/4: 1%), increased serum lipase (37%), nausea (49%; grade 3/4: 2%), vomiting (30%; grades 3/4: 1%)
Hematologic & oncologic: Decreased absolute lymphocyte count (91%; grades 3/4: 56%), decreased hemoglobin (51%; grades 3/4: <1%), decreased neutrophils (14%; grades 3/4: 2%), decreased platelet count (16%)
Hepatic: Increased serum alanine aminotransferase (≤65%), increased serum alkaline phosphatase (34%), increased serum aspartate aminotransferase (≤65%), increased serum bilirubin (27%)
Hypersensitivity: Cytokine release syndrome (89%)
Immunologic: Antibody development (29% to 33%)
Local: Skin edema (27%)
Nervous system: Chills (48%), dizziness (<20%), fatigue (64%), headache (31%), paresthesia (<20%)
Neuromuscular & skeletal: Arthralgia (22%), back pain (<20%), limb pain (<20%), muscle spasm (<20%), myalgia (<20%)
Renal: Increased serum creatinine (87%)
Respiratory: Dyspnea (<20%), flu-like symptoms (<20%), oropharyngeal pain (<20%)
Miscellaneous: Fever (76%)
Frequency not defined:
Hepatic: Hepatotoxicity
Hypersensitivity: Anaphylaxis
Nervous system: Brain edema
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to tebentafusp or any component of the formulation.
Concerns related to adverse effects:
• Cytokine release syndrome: Cytokine release syndrome (CRS) has occurred with tebentafusp administration and may be life-threatening. CRS signs/symptoms may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. In clinical studies, ≥ grade 2 CRS occurred in almost two-thirds to three-fourths of patients; some patients received systemic corticosteroids, supplemental oxygen, and/or a vasopressor for at least 1 infusion. Among patients who received >1 infusion, the median number of CRS events was 2 (range: 1 to 12). The majority of CRS episodes began the day of infusion; among cases that resolved, the median time to resolution was 2 days.
• Dermatologic toxicity: Skin reactions such as rash, pruritus, and cutaneous edema have been reported. Skin reactions have occurred in the majority of patients and have included grade 2 and grade 3 events. The median time to onset of skin reactions was 1 day (range: 1 to 55 days); the median time to improvement (to ≤ grade 1) was ~6 days.
• Hepatoxicity: Elevated ALT or AST were reported in approximately two-thirds of patients; the majority occurred within the first 3 tebentafusp infusions. In patients who experienced grade 3 or 4 transaminase elevations, most had improvement to ≤ grade 1 within 7 days. The median time to elevated liver enzymes (outside of CRS events) was 129 days.
Other warnings/precautions:
• Genotype testing: Select patients for treatment of unresectable or metastatic uveal melanoma with tebentafusp based on a positive HLA-A*02:01 genotyping test of a whole blood sample. Information on approved tests may be found at http://www.fda.gov/companiondiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Kimmtrak: Tebentafusp-tebn 100 mcg/0.5 mL (0.5 mL)
No
Solution (Kimmtrak Intravenous)
100 mcg/0.5 mL (per 0.5 mL): $24,312.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Kimmtrak: Tebentafusp-tebn 100 mcg/0.5 mL (0.5 mL)
Kimmtrak is available from specialty distributors. Information regarding access is available at https://kimmtrakhcp.com/KIMMTRAK-distribution-sheet.pdf.
IV: Administer over 15 to 20 minutes through a dedicated IV line using a sterile, nonpyrogenic, low protein-binding, 0.2-micron, in-line filter infusion set. Administer entire contents of infusion bag; after the infusion is completed, flush the line with an appropriate volume of sterile NS to ensure that the entire infusion volume/dose has been administered. If refrigerated, allow infusion bag to equilibrate to room temperature prior to infusion. Do not mix with other medications or administer other medications through the same IV line. Infusion should be completed within 4 hours of preparation (including infusion time).
Administer the first 3 tebentafusp infusions in an appropriate health care setting with immediate access to medications and resuscitative equipment to manage cytokine release syndrome. If no ≥ grade 2 hypotension (requiring medical intervention) during or after the third infusion, may administer subsequent doses in an ambulatory care setting. Monitor during the infusion and for at least 16 hours after infusion completion for the first 3 infusions; if infusions are tolerated, for subsequent infusions, monitor for a minimum of 30 minutes following infusion.
Uveal melanoma, unresectable or metastatic: Treatment of HLA-A*02:01-positive unresectable or metastatic uveal melanoma in adults.
Kimmtrak may be confused with Kymriah.
Tebentafusp may be confused with tagraxofusp.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
There are no known significant interactions.
Verify pregnancy status prior to therapy initiation in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for 1 week after the last tebentafusp dose.
Based on the mechanism of action, tebentafusp may cause fetal harm if administered during pregnancy.
It is not known if tebentafusp is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for at least 1 week after the last tebentafusp dose.
HLA-A*02:01 genotyping test of a whole blood sample. Monitor ALT, AST, and total bilirubin prior to tebentafusp initiation, as well as during treatment. Verify pregnancy status prior to treatment in patients who could become pregnant. Monitor fluid status, vital signs, and oxygenation level. Monitor closely for signs/symptoms of cytokine release syndrome (eg, fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, headache). Monitor for skin reactions such as rash, pruritus, and cutaneous edema. For the first 3 infusions, monitor during the infusion and for at least 16 hours after infusion completion; if infusions are tolerated, for subsequent infusions, monitor for a minimum of 30 minutes following infusion.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Tebentafusp is a bispecific T-cell engager; it consists of a soluble HLA-A*02:01-restricted T-cell receptor that is specific for the glycoprotein 100 (gp100) peptide and is fused to an anti-CD3 single-chain variable fragment (Nathan 2021). The T-cell receptor binds to a gp100 peptide presented by HLA-A*02:01 on the surface of uveal melanoma tumor cells. Once bound, they recruit and activate polyclonal T-cells (through CD3) to release inflammatory cytokines and cytolytic proteins, resulting in direct lysis of uveal melanoma tumor cells.
Distribution: Vdss: 7.56 L.
Metabolism: Catabolized into small peptides and amino acids.
Half-life elimination: Median: 7.5 hours (range: ~7 to 8 hours).
Excretion: Clearance: 16.4 L/day.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
