AE management
Cytokine release syndrome
- KIMMTRAK commonly causes mild to moderate CRS, which if not identified and treated appropriately, may become life-threatening or fatal1
- Most patients typically experienced CRS following each of the first 3 infusions.2 The majority (84%) of episodes of CRS started the day of infusion1
- A rise in temperature is generally the first sign of CRS, occurring earlier than drops in blood pressure. Once fever is detected, patients should be monitored more closely for changes in other vital signs like pulse rate, respiratory rate, and blood pressure.1 Consider managing symptoms early to help prevent CRS from escalating
- CRS symptoms were generally reversible and were mostly managed with IV fluids, NSAIDs, or systemic corticosteroids1,2
AE, adverse event; CRS, cytokine release syndrome.
- *For at least one infusion.
CRS grading and management guidance
No dosage reduction for KIMMTRAK is recommended. For specific dosage modifications please refer to Section 2.3, Table 1 in full Prescribing Information.1
ASTCT, American Society for Transplant and Cellular Therapy.
- *Based on ASTCT consensus grading of CRS criteria (Lee et al. 2019).1
- †If hypotension is not rapidly resolved (ie, within 2–3 hours of onset) with intravenous crystalloid therapy, intravenous corticosteroid therapy of methylprednisolone 2 mg/kg initial dose or equivalent and/or tocilizumab 8 mg/kg IV (not to exceed 800 mg/infusion) per institutional guidelines should be administered until symptoms (eg, hypotension) resolve.1,2
- ‡Do not escalate if severe CRS occurred during initial dose escalation; resume escalation once dosage is tolerated.1
Skin Reactions
Typically occurred following each of the first 3 infusions.2 Median time to onset was one day, with most resolved to ≤ grade 1 between doses.1
- Rash occurred in 83% of patients.1 Rash has been described as sunburn-like and may cause the skin to become red and itchy with the potential for blistering and peeling.3 It can manifest differently in different patients and affect part or all of the body3
- Monitor patients for skin reactions.1 If skin reactions occur, treat with antihistamines and topical or systemic steroids based on persistence and severity of symptoms
- Most systems resolved without any long-term sequelae.1 Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions1
- No cases of Stevens-Johnson syndrome or toxic epidermal necrolysis were reported4
- Rash is thought to be due to on-target off-tumor activity of KIMMTRAK against gp100-expressing healthy melanocytes in skin, consistent with the mechanism of action1,2
Elevated liver enzymes
The majority (73%) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations occurred within the first 3 infusions.1 Most patients experiencing grade 3 or 4 ALT/AST elevations had improvement to ≤ grade 1 within 7 days.1
- More than 90% of patients with ALT/AST elevation were able to continue treatment.7 Elevations in bilirubin have been reported in 27% of patients1
- Most of the elevations in bilirubin were temporarily associated with an increase in size of liver metastasis7
- Monitor ALT, AST, and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity1
Other adverse reactions1
Other adverse reactions* management and dose modifications1
- *Other adverse reactions as found in Section 6.1, Table 4 of full Prescribing Information.
- a Based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (NCI CTCAEv4.03).
CTCAE, Common Terminology Criteria for Adverse Events.
Indication
Important Safety Information Including Boxed Warning
KIMMTRAK is a bispecific gp100 peptide-HLA-directed CD3 T cell engager indicated for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.
WARNING: CYTOKINE RELEASE SYNDROME
Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated.
Indication and Important Safety Information Including Boxed Warning
Indication
KIMMTRAK is a bispecific gp100 peptide-HLA-directed CD3 T cell engager indicated for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.
Important Safety Information Including Boxed Warning
WARNING: CYTOKINE RELEASE SYNDROME
Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS occurred in 89% of patients who received KIMMTRAK with 0.8% being grade 3 or 4. Ensure immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS.
Skin ReactionsSkin reactions, including rash, pruritus, and cutaneous edema occurred in 91% of patients treated with KIMMTRAK. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions.
Elevated Liver Enzymes Elevations in liver enzymes occurred in 65% of patients treated with KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.
Embryo-Fetal ToxicityKIMMTRAK may cause fetal harm. Advise pregnant patients of potential risk to the fetus and patients of reproductive potential to use effective contraception during treatment with KIMMTRAK and 1 week after the last dose.
The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate.
Please see full Prescribing Information, including BOXED WARNING for CRS.