Version May 2024
Nasopharyngeal carcinoma, metastatic or recurrent, locally advanced (first-line treatment): IV: 240 mg once every 3 weeks (in combination with cisplatin and gemcitabine); continue until disease progression, unacceptable toxicity, or up to 24 months (Ref).
Nasopharyngeal carcinoma, recurrent unresectable or metastatic (previously treated): IV: 3 mg/kg once every 2 weeks; continue until disease progression or unacceptable toxicity (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Kidney impairment prior to treatment initiation:
CrCl ≥60 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, CrCl ≥60 mL/minute did not have a clinically meaningful effect on toripalimab pharmacokinetics.
CrCl ≥15 to <60 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (effects on toripalimab pharmacokinetics have not been studied).
CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.
Kidney toxicity during treatment:
Immune-mediated nephritis with kidney dysfunction: Note: If toripalimab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to ≤ grade 1, then follow with a corticosteroid taper and continue to taper over at least 1 month. Prednisone tapering recommendations when used for immune-mediated adverse reactions associated with immune checkpoint inhibitor therapy may be found in the prednisone monograph.
Grade 2 or 3 serum creatinine elevation: Withhold toripalimab; resume after complete or partial (to grade 0 or 1) resolution after corticosteroid taper. Permanently discontinue if no resolution within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
Grade 4 serum creatinine elevation: Permanently discontinue toripalimab.
Hepatic impairment prior to treatment initiation:
Mild impairment (total bilirubin >1 and ≤1.5 times ULN and any AST or total bilirubin ≤ ULN and AST > ULN): There are no dosage adjustments provided in the manufacturer's labeling; however, mild impairment did not have a clinically meaningful effect on toripalimab pharmacokinetics.
Moderate (total bilirubin >1.5 and ≤3 times ULN and any AST) or severe (total bilirubin >3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling (effects on toripalimab pharmacokinetics have not been studied).
Acute hepatotoxicity during treatment:
If toripalimab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to ≤ grade 1, then follow with a corticosteroid taper and continue to taper over at least 1 month. Prednisone tapering recommendations when used for immune-mediated adverse reactions associated with immune checkpoint inhibitor therapy may be found in the prednisone monograph.
Immune-mediated hepatitis without tumor involvement of the liver:
AST, ALT increases to >3 to ≤8 times ULN or total bilirubin >1.5 to ≤3 times ULN: Withhold toripalimab; resume after complete or partial (to grade 0 or 1) resolution after corticosteroid taper. Permanently discontinue if no resolution within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
AST or ALT >8 times ULN or total bilirubin >3 times ULN: Permanently discontinue toripalimab.
Immune-mediated hepatitis with tumor involvement of the liver: Note: If AST and ALT are ≤ ULN at baseline, follow recommendations for hepatitis with no liver involvement.
Baseline AST or ALT >1 to ≤3 times ULN and increases to >5 up to 10 times ULN or baseline AST or ALT >3 to ≤5 times ULN and increases to >8 up to 10 times ULN: Withhold toripalimab; resume after complete or partial (to grade 0 or 1) resolution after corticosteroid taper. Permanently discontinue if no resolution within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
Baseline AST or ALT is >ULN and increases to >10 times ULN or total bilirubin >3 times ULN: Permanently discontinue toripalimab.
Additional recommendations for hepatotoxicity during treatment:
Grade 2 immune-mediated hepatitis: Withhold immune checkpoint inhibitor (ICI); if no improvement within 3 to 5 days after ICI is withheld, consider initiation of corticosteroids (prednisone 0.5 to 1 mg/kg/day or equivalent) (Ref).
Grade 3 or 4 immune-mediated hepatitis: Withhold ICI; initiate corticosteroids (methylprednisolone 1 to 2 mg/kg or equivalent) (Ref). Based on data from a retrospective cohort study in patients with grade 3 or 4 immune-mediated hepatitis, initial treatment with methylprednisolone 1 mg/kg/day demonstrated similar time to ALT normalization (compared with higher methylprednisolone doses), while reducing the potential for corticosteroid-related complications (Ref).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: The dosing in the FDA-approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m2 experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).
Note: No dosage reduction of toripalimab is recommended. Other concomitant anticancer therapies may also require treatment interruption, dosage reduction, and/or discontinuation.
Immune-mediated adverse reactions (general information): Withhold toripalimab for severe (grade 3) immune-mediated adverse reactions. Permanently discontinue toripalimab for life-threatening (grade 4) immune-mediated adverse reactions, recurrent severe (grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or the inability to reduce corticosteroid dose to prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating corticosteroids. If toripalimab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) until improvement to ≤ grade 1; upon improvement to ≤ grade 1, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants if immune-mediated adverse reaction is not controlled with corticosteroid therapy. Systemic corticosteroids may not be necessary for certain adverse reactions. Hormone-replacement therapy may be required for endocrinopathies (if clinically indicated). See table for additional dosage modification guidance.
Additional management recommendations: Consider withholding immune checkpoint inhibitor (ICI) therapy for most grade 2 toxicities and resume when symptoms and/or lab values resolve to ≤ grade 1; systemic corticosteroids (initial dose of 0.5 to 1 mg/kg/day prednisone [or equivalent]) may be administered if indicated for grade 2 toxicities (Ref). Refer to guideline for further information regarding management of immune-mediated adverse reactions associated with ICI therapy.
|
Adverse reaction |
Severity |
Toripalimab dosage modification |
|---|---|---|
|
a SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; DRESS = drug rash with eosinophilia and systemic symptoms. | ||
|
b Prednisone tapering recommendations when used for immune-mediated adverse reactions associated with immune checkpoint inhibitor therapy may be found in the prednisone monograph. | ||
|
Immune-mediated adverse reactions | ||
|
Cardiovascular toxicity: Myocarditis |
Grade 2, 3, or 4 |
Permanently discontinue toripalimab. |
|
Dermatologic toxicity |
Mild or moderate nonexfoliative rash |
May be managed with topical emollients and/or topical corticosteroids. |
|
Exfoliative dermatologic conditions: suspected SJS, TEN, or DRESSa |
Withhold toripalimab; resume after complete or partial (to grade 0 or 1) resolution after corticosteroid taper.b Permanently discontinue if no resolution within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. | |
|
Confirmed SJS, TEN, or DRESS |
Permanently discontinue toripalimab. | |
|
Endocrinopathies |
Grade 3 or 4 |
Withhold toripalimab until clinically stable or permanently discontinue depending on severity. Resume after complete or partial (to grade 0 or 1) resolution after corticosteroid taper.b Permanently discontinue if no resolution within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Adrenal insufficiency, ≥ grade 2 |
Initiate symptomatic management, including hormone replacement, as clinically indicated. Withhold or permanently discontinue toripalimab depending on severity. | |
|
Diabetes, type 1 |
Initiate insulin as clinically indicated. Withhold or permanently discontinue toripalimab depending on severity. | |
|
Hypophysitis |
Initiate hormone-replacement therapy as clinically indicated. Withhold or permanently discontinue toripalimab depending on severity. | |
|
Hyperthyroidism |
Initiate medical management as clinically indicated. Withhold or permanently discontinue toripalimab depending on severity. | |
|
Hypothyroidism |
Initiate thyroid hormone-replacement therapy as clinically indicated. Withhold or permanently discontinue toripalimab depending on severity. | |
|
Thyroiditis |
Withhold or permanently discontinue toripalimab depending on severity. | |
|
GI toxicity: Colitis |
Grade 2 or 3 |
Withhold toripalimab; resume after complete or partial (to grade 0 or 1) resolution after corticosteroid taper.b Permanently discontinue if no resolution within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grade 4 |
Permanently discontinue toripalimab. | |
|
Neurologic toxicities |
Grade 2 |
Withhold toripalimab; resume after complete or partial (to grade 0 or 1) resolution after corticosteroid taper.b Permanently discontinue if no resolution within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grade 3 or 4 |
Permanently discontinue toripalimab. | |
|
Ocular disorders: Vogt-Koyanagi-Harada–like syndrome |
Any |
May require systemic corticosteroids to reduce the risk of permanent vision loss. |
|
Pulmonary toxicity: Pneumonitis |
Grade 2 |
Withhold toripalimab; resume after complete or partial (to grade 0 or 1) resolution after corticosteroid taper.b Permanently discontinue if no resolution within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grade 3 or 4 |
Permanently discontinue toripalimab. | |
|
Other adverse reactions | ||
|
Infusion-related reactions |
Grade 1 or 2 |
Interrupt or slow the rate of toripalimab infusion. |
|
Grade 3 or 4 |
Stop infusion. Permanently discontinue toripalimab. | |
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%:
Dermatologic: Pruritus (11%), skin rash (11%)
Endocrine & metabolic: Decreased serum albumin (38%), decreased serum calcium (29%), decreased serum phosphate (32%), decreased serum sodium (35%), hypothyroidism (15% to 27%), increased serum glucose (24%), increased serum triglycerides (26%), weight loss (11%)
Gastrointestinal: Constipation (11%), decreased appetite (13%)
Hematologic & oncologic: Decreased hemoglobin (43%; grades 3/4: 6% to 7%), lymphocytopenia (52%; grades 3/4: 8% to 9%)
Hepatic: Increased serum alanine aminotransferase (23%), increased serum alkaline phosphatase (28%), increased serum aspartate aminotransferase (30%)
Nervous system: Fatigue (22%)
Neuromuscular & skeletal: Musculoskeletal pain (18% to 20%)
Respiratory: Cough (20%)
Miscellaneous: Fever (16%)
1% to 10%:
Dermatologic: Dermatologic disorder (4%)
Endocrine & metabolic: Hyperthyroidism (7%)
Gastrointestinal: Increased serum amylase (grades 3/4: 3%), increased serum lipase (grades 3/4: 4%)
Hematologic & oncologic: Decreased serum fibrinogen (grades 3/4: 5%)
Hepatic: Abnormal liver function (3%), hepatitis (3%), hyperbilirubinemia (2%)
Hypersensitivity: Infusion-related reaction (2%)
Immunologic: Antibody development (4%)
Respiratory: Pneumonia (5%), pneumonitis (3%)
<1%:
Endocrine & metabolic: Adrenocortical insufficiency, hypophysitis, thyroiditis, type 1 diabetes mellitus
Gastrointestinal: Colitis
Renal: Nephritis
Frequency not defined:
Cardiovascular: Myocarditis, pericardial effusion, pericarditis, vasculitis
Endocrine & metabolic: Hypoparathyroidism
Gastrointestinal: Duodenitis, gastritis, pancreatitis
Hematologic & oncologic: Anemia, aplastic anemia, hemolytic anemia, hemophagocytic lymphohistiocytosis, immune thrombocytopenia, lymphadenitis (histiocytic necrotizing lymphadenitis [Kikuchi lymphadenitis]), thrombocytopenia
Immunologic: Dermatomyositis, organ transplant rejection (solid), sarcoidosis
Infection: Systemic inflammatory response syndrome
Nervous system: Demyelinating disease, encephalitis, Guillain-Barré syndrome, meningitis, myasthenia (myasthenic syndrome), myasthenia gravis (including exacerbation), neuropathy (autoimmune), paresis (nerve)
Neuromuscular & skeletal: Arthritis, myelitis, myositis, polymyalgia rheumatica, polymyositis, rhabdomyolysis
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Adverse reactions (immune mediated): PD-1/PD-L1 blockers (including toripalimab) potentially break peripheral tolerance and induce immune-mediated adverse reactions. Immune-mediated adverse reactions, which can be severe or fatal, may occur in any organ system or tissue and may affect more than one organ system simultaneously. Immune-mediated adverse reactions may occur at any time after toripalimab initiation. While immune-mediated adverse reactions generally manifest during treatment, they may also occur after toripalimab discontinuation. Early identification and management of immune-mediated adverse reactions are necessary to ensure safe use of toripalimab. If suspected immune-mediated reactions occur, initiate appropriate workup to exclude alternative causes (including infection). Medically manage immune-mediated adverse reactions promptly and refer for specialty consultation as appropriate.
• Cardiotoxicity: Myocarditis, pericarditis, vasculitis, and pericardial effusion have been reported.
• Dermatologic toxicity: Toripalimab can cause immune-mediated rash or dermatitis. Grades 2 and 3 immune-mediated skin reactions were observed. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), has occurred with anti-PD-1/PD-L1 monoclonal antibodies. Immune-mediated dermatologic reactions were treated with systemic corticosteroids in up to one-fourth of patients. While immune-mediated dermatologic reactions led to treatment interruption and/or discontinuation in some cases, dermatologic reactions resolved in a majority of patients.
• Endocrinopathies: Toripalimab is associated with immune-mediated endocrinopathies.
- Adrenal insufficiency: Toripalimab can cause primary and secondary adrenal insufficiency. Grades 1 and 2 adrenal insufficiency have been observed. May require hormonal replacement therapy; three-fourths of affected patients required systemic corticosteroids. Adrenal insufficiency led to treatment interruption in one case and was reinitiated upon symptom improvement.
- Diabetes mellitus: Type 1 diabetes mellitus (which may present with diabetic ketoacidosis) was observed rarely, including grades 2 to 4 events. Insulin may be required, including long-term therapy.
- Hypophysitis: Toripalimab can cause immune-mediated hypophysitis, which may present with acute mass-effect symptoms (headache, photophobia, or visual field defects). Hypophysitis may lead to hypopituitarism. Cases of grades 2 and 3 hypophysitis were reported; all cases required systemic corticosteroids. Toripalimab was withheld and reinitiated in one case although hypophysitis led to permanent discontinuation in another case.
- Thyroid disorders: Toripalimab can cause immune-mediated thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Grade 2 hyperthyroidism has been observed and resolved in most cases. Hypothyroidism (including grades 1 and 2 events) has occurred with toripalimab; treatment interruption was required in a small number of patients; most were able to reinitiate treatment. A majority of cases required thyroid hormone replacement therapy. Hypothyroidism may follow hyperthyroidism. Thyroiditis was observed (including grade 2 cases) and may present with or without endocrinopathy; thyroiditis resolved in some cases.
• GI toxicity: Toripalimab can cause immune-mediated colitis, which may present as diarrhea. Cases of grades 2 and 3 colitis were reported; colitis resolved in all cases. Cytomegalovirus infection/reactivation has been observed in patients with corticosteroid-refractory immune-mediated colitis. Pancreatitis (including increased serum amylase and lipase levels), gastritis, and duodenitis have also been reported.
• Hepatotoxicity: Toripalimab can cause immune-mediated hepatitis. Hepatitis was reported in a small percentage of patients, including grades 2 to 4 events. Systemic corticosteroids were used in a patient with grade 3 immune-mediated hepatitis treated with toripalimab in combination with chemotherapy. While immune-mediated hepatitis led to discontinuation in a small percentage of patients, hepatitis resolved in approximately half of patients.
• Infusion-related reactions: Severe or life-threatening infusion-related reactions have been reported with toripalimab, including hypersensitivity and anaphylaxis. Grade 2 and 3 events have been observed.
• Kidney toxicity: Toripalimab can cause immune-mediated nephritis and kidney dysfunction. Grades 3 and 4 events were observed. Some cases of immune-mediated nephritis required systemic corticosteroids. Nephritis led to discontinuation in one case. Nephritis resolved in a majority of patients.
• Ocular toxicity: Uveitis, iritis, and other ocular inflammatory toxicities may occur with anti-PD-1/PD-L1 monoclonal antibodies (some cases may be associated with retinal detachment). Various grades of visual impairment (including blindness) can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome.
• Pulmonary toxicity: Toripalimab can cause immune-mediated pneumonitis, including rare fatal events. Grade ≥2 immune-mediated pneumonitis was reported in a small percentage of patients with toripalimab either as a single agent, or in combination with chemotherapy. Most patients experiencing pneumonitis required management with systemic corticosteroids. Pneumonitis resolved in some of the affected patients and led to discontinuation in a small percentage of patients. In patients treated with other anti-PD-1/PD-L1 monoclonal antibodies, the incidence of pneumonitis was higher in patients with a history of prior thoracic radiation.
• Other immune-mediated toxicities: Other clinically relevant immune-mediated disorders have been observed rarely with toripalimab (or other anti-PD-1/PD-L1 monoclonal antibodies) and may be severe or fatal, including meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy, myositis/polymyositis, rhabdomyolysis (and associated sequelae including kidney failure), arthritis, polymyalgia rheumatica, dermatomyositis, hypoparathyroidism, hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, and solid organ transplant rejection.
Disease-related concerns:
• Hematopoietic cell transplantation: Fatal and other serious complications may occur in patients who receive allogeneic hematopoietic cell transplant (HCT) before or after treatment with an anti-PD-L1/PD-1 monoclonal antibody. Transplant-related complications included hyperacute graft-vs-host disease (GVHD), acute or chronic GVHD, hepatic veno-occlusive disease (also known as sinusoidal obstruction syndrome) after reduced-intensity conditioning, and steroid-requiring febrile syndrome (with no identified infectious etiology). These complications may occur despite intervening therapy between PD-L1/PD-1 blockade and HCT. Manage early signs/symptoms of transplant-related complications promptly. Assess the risks/benefits of treatment with an anti-PD-L1/PD-1 monoclonal antibody prior to or after an allogenic HCT.
• Myasthenia gravis: Immune checkpoint inhibitors (ICIs) may worsen or precipitate new myasthenia gravis (MG), especially within the first 16 weeks of treatment; use with caution. Patients with well-controlled MG may be considered for ICI therapy if MG treatment is maintained (or reinitiated in patients whose MG is in remission), combination therapy (eg, anti–CTLA-4 with anti–PD-L/PD-L1 monoclonal antibodies) is avoided, and respiratory and bulbar function are closely followed. In patients who develop overt MG during ICI therapy, early aggressive treatment with plasma exchange or intravenous immunoglobulin in combination with high-dose corticosteroids may be required (AAN [Narayanaswami 2021]).
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and kidney and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Loqtorzi: Toripalimab-tpzi 240 mg/6 mL (40 mg/mL) (6 mL) [contains polysorbate 80]
No
Solution (Loqtorzi Intravenous)
240 mg/6 mL (per mL): $1,778.41
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IV: Administer the first infusion over at least 60 minutes; if no infusion-related reactions occurred with the first infusion, administer subsequent infusions over 30 minutes. Administer via an infusion pump using an inline 0.2- or 0.22-micron filter. Do not administer other medications through the same infusion line. Toripalimab is compatible with polypropylene infusion sets with 0.2- or 0.22-micron inline filters.
Concomitant chemotherapy: When administered on the same day as chemotherapy, administer toripalimab prior to chemotherapy.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Loqtorzi: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761240s000lbl.pdf#page=24
Nasopharyngeal carcinoma, metastatic or recurrent, locally advanced: First-line treatment (in combination with cisplatin and gemcitabine) of metastatic or with recurrent, locally advanced nasopharyngeal carcinoma (NPC) in adults.
Nasopharyngeal carcinoma, recurrent unresectable or metastatic: Treatment (as a single agent) of recurrent unresectable or metastatic NPC in adults with disease progression on or after a platinum-containing chemotherapy.
Toripalimab may be confused with cemiplimab, dostarlimab, nivolumab/relatlimab, retifanlimab, tafasitamab, tisotumab vedotin, tocilizumab, tremelimumab.
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.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetaminophen: May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Antibiotics: May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Corticosteroids (Systemic): May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Management: Carefully consider the need for corticosteroids, at doses of a prednisone-equivalent of 10 mg or more per day, during the initiation of immune checkpoint inhibitor therapy. Use of corticosteroids to treat immune related adverse events is still recommended Risk D: Consider therapy modification
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Inhibitors of the Proton Pump (PPIs and PCABs): May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Ketoconazole (Systemic): Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may enhance the hepatotoxic effect of Ketoconazole (Systemic). Risk C: Monitor therapy
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Verify pregnancy status prior to use in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during therapy and for 4 months after the last toripalimab dose.
Animal reproduction studies have not been conducted. Based on the mechanism of action, in utero exposure to toripalimab may cause fetal harm. Immune-mediated rejection of the fetus and fetal death were observed following inhibition of the PD-1/PD-L1 pathway in animal models.
Toripalimab is a humanized monoclonal antibody (IgG4). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).
It is not known if toripalimab is present in breast milk.
Toripalimab is a humanized monoclonal antibody (IgG4). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021). Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 4 months after the last dose of toripalimab.
Monitor hepatic function (ALT, AST, and total bilirubin; baseline and periodically during treatment), kidney function (serum creatinine; baseline and periodically during treatment), and thyroid function (baseline and periodically during treatment); monitor blood glucose (for hyperglycemia). Verify pregnancy status prior to treatment initiation in patients who could become pregnant. Monitor closely for signs/symptoms of immune-mediated adverse reactions, including adrenal insufficiency, hypophysitis, thyroid disorders, diabetes mellitus, diarrhea/colitis (consider initiating or repeating infectious workup in patients with corticosteroid-refractory immune-mediated colitis to exclude alternative causes), myocarditis, pneumonitis, rash/dermatologic toxicity, neurotoxicity, and ocular disorders. If suspected immune-mediated reactions occur, initiate appropriate workup to exclude alternative causes (including infection). If received/receiving hematopoietic cell transplant, monitor closely for early signs/symptoms of transplant-related complications. Monitor for signs/symptoms of infusion-related reactions (eg, rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, fever).
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.
Additional suggested monitoring (ASCO [Schneider 2021]):
Prior to therapy: CBC with differential, serum chemistries, creatine kinase, comprehensive clinical assessment including performance status, weight, BMI, heart rate, BP, and oxygen saturation; consider chest x-ray, electrocardiogram, and CT scan; assess history of autoimmune conditions, organ-specific disease, endocrinopathies, neuropathy, and infectious disease; assess bowel habits, respiratory symptoms, skin (for rash), arthralgias, and neurologic symptoms.
During therapy: Assess BP, weight, heart rate, and oxygen saturation; assess for infections, screen for hyperglycemia/diabetes (polyuria, polydipsia, weight loss); eye exam (including intraocular pressure after 6 weeks), CBC with differential, serum chemistries, and creatine kinase; monitor bone mineral density (with long-term therapy).
Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]). Obtain baseline ECG, natriuretic peptides, and troponins in all patients; obtain a baseline echocardiogram in high-risk patients; consider serial ECGs and cardiac troponins prior to doses 2, 3, and 4, and if normal, reduce to every 3 doses until completion of therapy; cardiovascular risk assessment every 6 to 12 months in high-risk patients who require long-term (>12 months) therapy, consider cardiovascular risk assessment every 6 to 12 months in all patients requiring long-term therapy (ESC [Lyon 2022]). Refer to a cardiologist when clinically indicated.
Toripalimab is a humanized IgG4 monoclonal antibody that inhibits programmed death receptor-1 (PD-1). PD-L1 and PD-L2 binding to the PD-1 receptor found on T cells inhibits T-cell proliferation and cytokine production. Toripalimab binds to the PD-1 receptor found on T cells, blocking interaction with the ligands PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of immune response, including antitumor response. Upregulation of PD-1 ligands occurs in some tumors, therefore signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors.
Distribution: Vdss: 3.7 L.
Metabolism: Metabolized into small peptides via catabolic pathways.
Half-life elimination: 10 ± 1.5 days (following the first dose) and 18 ± 9.4 days (at steady state).
Excretion: Clearance: 14.9 mL/hour (following the first dose) and 9.5 mL/hour (at steady state).
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