Retifanlimab: Drug information

For additional information see "Retifanlimab: Patient drug information"

For abbreviations, symbols, and age group definitions show table

Brand Names: US

Zynyz

Pharmacologic Category

Antineoplastic Agent, Anti-PD-1 Monoclonal Antibody;
Antineoplastic Agent, Immune Checkpoint Inhibitor;
Antineoplastic Agent, Monoclonal Antibody

Dosing: Adult

Anal cancer, squamous cell carcinoma, locally recurrent or metastatic

Anal cancer, squamous cell carcinoma, locally recurrent or metastatic:

First-line treatment: IV: 500 mg once every 4 weeks (in combination with carboplatin and paclitaxel) for 6 cycles, followed by 500 mg once every 4 weeks (as a single agent); continue disease progression, unacceptable toxicity, or up to 12 months (Ref).

Previously treated: IV: 500 mg once every 4 weeks; continue until disease progression, unacceptable toxicity, or up to 24 months (Ref).

Merkel cell carcinoma, metastatic or recurrent locally advanced

Merkel cell carcinoma, metastatic or recurrent locally advanced: IV: 500 mg once every 4 weeks; continue until disease progression, unacceptable toxicity, or up to 24 months (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Kidney impairment prior to treatment initiation:

eGFR ≥26 mL/minute/1.73 m²: There are no dosage adjustments provided in the manufacturer's labeling; however, eGFR ≥26 mL/minute/1.73 m²did not have a clinically meaningful effect on retifanlimab pharmacokinetics.

eGFR <26 mL/minute/1.73 m²: There are no dosage adjustments provided in the manufacturer's labeling (effects on retifanlimab pharmacokinetics are unknown).

Kidney toxicity during treatment:

Immune-mediated nephritis with kidney dysfunction: General information: If retifanlimab 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 over at least 1 month. Consider administration of other systemic immunosuppressants if immune-mediated adverse reaction is not controlled with corticosteroid therapy (Ref).

**Retifanlimab** **Recommended Dosage Modifications for Acute Immune-Mediated Nephritis During Treatment**
Adverse reaction	Severity^a	Retifanlimab dosage modification^b
^a Serum creatinine elevation grade levels (NCI CTCAE version 5): Grade 0 or 1: Serum creatinine ≤1.5 × baseline; serum creatinine ≤1.5 × ULN Grade 2: Serum creatinine >1.5 to 3 × baseline; serum creatinine >1.5 to ≤3 × ULN Grade 3: Serum creatinine >3 × baseline; serum creatinine >3 to ≤6 × ULN Grade 4: Serum creatinine >6 × ULN
^bManufacturer’s labeling.
^c Refer to prednisone monograph for tapering recommendations when used for immune-mediated adverse reactions associated with checkpoint inhibitor therapy.
Immune-mediated nephritis with kidney dysfunction	Grade 2 or 3^aserum creatinine elevation	Withhold retifanlimab; resume retifanlimab after complete or partial (to grade 0 or 1^a) resolution after corticosteroid taper.^c Permanently discontinue retifanlimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.^b
Immune-mediated nephritis with kidney dysfunction	Grade 4^a serum creatinine elevation	Permanently discontinue retifanlimab.^b

Dosing: Liver Impairment: Adult

Hepatic impairment prior to treatment initiation:

Mild impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 and ≤1.5 × ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling; however, mild impairment did not have a clinically meaningful effect on retifanlimab pharmacokinetics.

Moderate or severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (effects on retifanlimab pharmacokinetics are unknown).

Acute hepatotoxicity during treatment:

General information: Abnormal liver enzymes should be evaluated to differentiate immune-mediated adverse reactions from other etiologies (eg, new or progressive liver metastases, viral hepatitis, thromboembolism) (Ref). If retifanlimab 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 over at least 1 month. Consider administration of other systemic immunosuppressants if immune-mediated adverse reaction is not controlled with corticosteroid therapy (Ref).

**Retifanlimab** **Recommended Dosage Modifications for Acute Immune-Mediated Hepatoxicity During Treatment**
Adverse reaction	Severity	Retifanlimab dosage modification
^aManufacturer’s labeling.
^bRefer to prednisone monograph for tapering recommendations when used for immune-mediated adverse reactions associated with checkpoint inhibitor therapy.
^c ASCO (Schneider 2021).
^d Li 2022.
Immune-mediated hepatitis without tumor involvement of the liver	AST or ALT >3 up to 8 × ULN or total bilirubin >1.5 up to 3 × ULN	Withhold retifanlimab; resume retifanlimab after complete or partial (to grade 0 or 1 [AST or ALT ≤3 × ULN or total bilirubin ≤1.5 × ULN]) resolution after corticosteroid taper.^a,b Permanently discontinue retifanlimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.^a
	Single-agent therapy: AST or ALT >3 up to 5 × ULN and/or total bilirubin >1.5 up to 3 × ULN	*Guideline recommendations*: Withhold retifanlimab. Delayed initiation of lower dose corticosteroids (0.5 to 1 mg/kg/day prednisone [or equivalent]) may be considered if no improvement following 3 to 5 days of treatment interruption.^c
	AST or ALT >8 × ULN or total bilirubin >3 × ULN	Permanently discontinue retifanlimab^a
	Single-agent therapy: AST or ALT >5 × ULN and/or total bilirubin >3 × ULN or Symptomatic liver dysfunction, fibrosis (biopsy confirmed), compensated/ decompensated cirrhosis, or reactivation of chronic hepatitis	*Guideline recommendations*: Withhold immune checkpoint inhibitor; immediately initiate corticosteroids (methylprednisolone 1 to 2 mg/kg or equivalent). Consider permanent discontinuation if asymptomatic, permanently discontinue retifanlimab if symptomatic.^c 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.^d
Immune-mediated hepatitis with tumor involvement of the liver Note: If AST and ALT are ≤ ULN at baseline, follow recommendations for hepatitis without tumor involvement of the liver.	Baseline AST or ALT >1 up to 3 × ULN and increases to >5 up to 10 × ULN or Baseline AST or ALT >3 up to 5 × ULN and increases to >8 up to 10 × ULN	Withhold retifanlimab; resume retifanlimab after complete or partial (to grade 0 or 1 [AST or ALT ≤3 × ULN]) resolution after corticosteroid taper.^a,b Permanently discontinue retifanlimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.^a
	AST or ALT increases to >10 × ULN or total bilirubin increases to >3 × ULN	Permanently discontinue retifanlimab^a

Dosing: Obesity: Adult

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/m²experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).

Dosing: Adjustment for Toxicity: Adult

Note: No dosage reduction of retifanlimab is recommended. Other concomitant anticancer therapies may also require treatment interruption, dosage reduction, and/or discontinuation.

Immune-mediated adverse reactions (general information): Withhold retifanlimab for severe (grade 3) immune-mediated adverse reactions. Permanently discontinue retifanlimab 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 retifanlimab 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 guideline-based management recommendations: Consider withholding immune checkpoint inhibitor (ICI) therapy for select grade 1 toxicities (eg, aseptic meningitis, encephalitis, immune-mediated neuropathy, aplastic anemia, acquired hemophilia A, acquired thrombotic thrombocytopenic purpura [TTP], troponin elevation). For most grade 2 toxicities, consider withholding checkpoint inhibitor therapy 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.

**Retifanlimab Recommended Dosage Modifications for Adverse Reactions**
Adverse reaction	Severity	Retifanlimab dosage modification
^a SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; DRESS = drug rash with eosinophilia and systemic symptoms.
^b Refer to Prednisone monograph for tapering recommendations when used for immune-mediated adverse reactions associated with immune checkpoint inhibitor therapy.
Immune-mediated adverse reactions
Cardiovascular toxicity: Myocarditis	Grade 2, 3, or 4	Permanently discontinue retifanlimab.
Dermatologic toxicity	Mild or moderate nonexfoliative rash	May be managed with topical emollients and/or topical corticosteroids.
	Exfoliative dermatologic conditions: Grade 3 or suspected SJS, TEN, or DRESS^a	Withhold retifanlimab; 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 or confirmed SJS, TEN, or DRESS	Permanently discontinue retifanlimab.
Endocrinopathies	Grade 2	Depending on the severity, consider withholding retifanlimab until symptom improvement with hormone replacement; resume once acute symptoms have resolved.
	Grade 3 or 4	Withhold retifanlimab until clinically stable or permanently discontinue depending on severity.
	Adrenal insufficiency, ≥ grade 2	Initiate symptomatic management (per institutional protocol, including hormone replacement as clinically indicated). Depending on the severity, withhold or permanently discontinue retifanlimab.
	Diabetes, type 1	Initiate insulin as clinically indicated. Depending on the severity, withhold retifanlimab.
	Hypophysitis	Withhold or discontinue retifanlimab (depending on the severity). Initiate hormone-replacement therapy as clinically indicated.
	Hyperthyroidism/Thyroiditis	Withhold or discontinue retifanlimab (depending on the severity). Initiate medical management as clinically indicated.
	Hypothyroidism	Withhold or discontinue retifanlimab (depending on the severity). Initiate thyroid hormone-replacement therapy as clinically indicated.
	Thyroiditis	Withhold or discontinue retifanlimab (depending on the severity). Initiate hormone replacement therapy or medical management as clinically indicated.
GI toxicity: Colitis	Grade 2 or 3	Withhold retifanlimab; 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.
GI toxicity: Colitis	Grade 4	Permanently discontinue retifanlimab.
Neurologic toxicities	Grade 2	Withhold retifanlimab; 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.
Neurologic toxicities	Grade 3 or 4	Permanently discontinue retifanlimab.
Ocular disorders: Vogt-Koyanagi-Harada–like syndrome		May require systemic corticosteroids to reduce the risk of permanent vision loss.
Pulmonary toxicity: Pneumonitis	Grade 2	Withhold retifanlimab; 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.
Pulmonary toxicity: Pneumonitis	Grade 3 or 4	Permanently discontinue retifanlimab.
Other adverse reactions
Infusion-related reactions	Grade 1 or 2	Interrupt or slow the rate of retifanlimab infusion.
Infusion-related reactions	Grade 3 or 4	Permanently discontinue retifanlimab.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults. Reactions listed may be reported for other agents in the same pharmacological class (PD-1/PD-L1-blocking antibodies) and may not be specifically reported for retifanlimab.

>10%:

Dermatologic: Pruritus (12% to 18%), skin rash (8% to 16%; including acneiform eruption, dermatitis, eczema, erythema of skin, maculopapular rash, palmar-plantar erythrodysesthesia)

Endocrine & metabolic: Decreased serum albumin (36%), decreased serum sodium (23% to 24%), increased serum triglycerides (19%)

Gastrointestinal: Abdominal pain (14%), constipation (15%), decreased appetite (15%), diarrhea (15% to 23%; grades 3/4: 2%), increased serum amylase (19%), increased serum lipase (17% to 30%), nausea (10% to 16%), vomiting (14%; grades 3/4: 1%)

Genitourinary: Perineal pain (19%), urinary tract infection (17%)

Hematologic & oncologic: Decreased hemoglobin (35% to 38%; grades 3/4: 1% to 2%), decreased neutrophils (13%; grades 3/4: 3%), hemorrhage (19%; grades 3/4: 3%), leukopenia (12%; grades 3/4: 1%), lymphocytopenia (29% to 33%; grades 3/4: 6% to 10%)

Hepatic: Increased serum alanine aminotransferase (16% to 21%), increased serum alkaline phosphatase (20%), increased serum aspartate aminotransferase (23% to 28%)

Infection: Infection (21%; including anal abscess, cellulitis, cholangitis, cholecystitis, herpes zoster infection, Lyme disease, pelvic region infection, peritonitis, pneumonia, pneumonia due to Pneumocystis jirovecii, postoperative wound infection, pseudomonas infection, sepsis, skin infection, wound infection)

Nervous system: Fatigue (28% to 42%; including asthenia)

Neuromuscular & skeletal: Musculoskeletal pain (22% to 27%; including arthralgia, back pain, limb pain, musculoskeletal chest pain, myalgia, neck pain, noncardiac chest pain, ostealgia, osteoarthritis)

Respiratory: Cough (13%), dyspnea (14%)

Miscellaneous: Fever (10% to 14%)

1% to 10%:

Endocrine & metabolic: Decreased serum potassium (9%), hyperthyroidism (6%), hypothyroidism (10%), increased serum calcium (8%), weight loss (10%)

Gastrointestinal: Colitis (2%)

Hepatic: Hepatitis (3%), increased serum bilirubin (8%)

Nervous system: Headache (10%)

Renal: Nephritis (2%)

Respiratory: Pneumonitis (3%)

<1%:

Cardiovascular: Myocarditis, pericarditis, vasculitis

Endocrine & metabolic: Adrenocortical insufficiency, hypoparathyroidism, hypophysitis, thyroiditis, type 1 diabetes mellitus

Gastrointestinal: Duodenitis, gastritis, pancreatitis

Hematologic & oncologic: Aplastic anemia, hemolytic anemia, hemophagocytic lymphohistiocytosis, immune thrombocytopenia, lymphadenitis (histiocytic necrotizing lymphadenitis [Kikuchi lymphadenitis])

Hypersensitivity: Infusion-related reaction (grade 3)

Immunologic: Organ transplant rejection (corneal graft, solid), sarcoidosis

Infection: Systemic inflammatory response syndrome

Nervous system: Demyelinating disease, encephalitis, Guillain-Barré syndrome, meningitis, myasthenia (myasthenic syndrome), myasthenia gravis (including exacerbation of myasthenia gravis), myelitis, neuropathy (autoimmune), paresis (nerve)

Neuromuscular & skeletal: Arthritis, myositis, polymyalgia rheumatica, polymyositis, rhabdomyolysis

Ophthalmic: Iritis, uveitis

Frequency not defined:

Cardiovascular: Atrial fibrillation, cardiac arrhythmia

Nervous system: Nerve root disorder, peripheral demyelinating polyneuropathy

Neuromuscular & skeletal: Fascia disease (eosinophilic fasciitis)

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Adverse reactions (immune mediated): Retifanlimab potentially breaks peripheral tolerance and induces immune-mediated adverse reactions. Severe and fatal immune-mediated adverse reactions may occur in any organ system or tissue. Reactions generally occur during treatment (may occur at any time after retifanlimab initiation); reactions may also occur after retifanlimab discontinuation. Early identification and management of immune-mediated adverse reactions are necessary to ensure safe use of retifanlimab. 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, and vasculitis have been reported.

• Dermatologic toxicity: Retifanlimab can cause immune-mediated rash or dermatitis. Grades 2 and 3 immune-mediated skin reactions were observed. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms, has occurred with anti-PD-1/PD-L1 monoclonal antibodies. Immune-mediated dermatologic reactions were treated with systemic corticosteroids in one-fourth of patients, and reactions resolved in three-fourths of those patients. In cases where retifanlimab was withheld for dermatologic toxicity, a majority reinitiated treatment after symptom improvement, and immune-mediated dermatologic toxicity recurred in one case.

• Endocrinopathies: Retifanlimab is associated with immune-mediated endocrinopathies.

- Adrenal insufficiency: Retifanlimab (as a single agent or in combination with carboplatin and paclitaxel) can cause primary and secondary adrenal insufficiency. Grades 2 and 3 adrenal insufficiency have been observed. May require hormonal replacement therapy; all affected patients required systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation rarely. Adrenal insufficiency resolved in almost one-half of patients.

- Diabetes mellitus: Type 1 diabetes mellitus (which may present with diabetic ketoacidosis) was observed rarely, including a grade 3 event requiring treatment interruption. Insulin therapy may be required.

- Hypophysitis: Retifanlimab 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 hypophysitis were reported. Both hypophysitis cases required systemic corticosteroids. Hypophysitis resolved in one of the cases.

- Thyroid disorders: Retifanlimab can cause immune-mediated thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Grade 2 hyperthyroidism has been observed. Systemic corticosteroids were required in some patients with hyperthyroidism, and endocrine therapy was required in nearly half of patients, although hyperthyroidism rarely required treatment interruption. Hypothyroidism (including grade 2 events) has occurred with retifanlimab; while a few cases required treatment interruption, they did not require treatment discontinuation; one case required systemic corticosteroids and most cases required endocrine therapy. Hypothyroidism may follow hyperthyroidism. Thyroiditis was observed (grade 1 cases) and may present with or without endocrinopathy; thyroiditis did not require treatment interruption or discontinuation and resolved in one-third of cases.

• GI toxicity: Retifanlimab can cause immune-mediated colitis. Cases of grades 2, 3, and 4 colitis were reported with retifanlimab (as a single agent or in combination with carboplatin and paclitaxel). Systemic corticosteroids were administered to most patients for immune-mediated colitis. Most patients with colitis experienced resolution. In cases where retifanlimab was withheld for colitis, some patients reinitiated treatment after symptom improvement and did not experience recurrence. Cytomegalovirus infection/reactivation has been observed in patients with corticosteroid-refractory immune-mediated colitis who were treated with anti-PD-1/PD-L1 monoclonal antibodies. Pancreatitis (including increased serum amylase and lipase levels), gastritis, and duodenitis have also been reported.

• Hepatotoxicity: Retifanlimab 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 most patients experiencing immune-mediated hepatitis. Hepatitis resolved in approximately half of patients. In cases where retifanlimab was withheld for hepatitis, some patients reinitiated treatment after symptom improvement; hepatitis recurred in 50% of these patients.

• Infusion-related reactions: Severe infusion-related reaction occurred rarely with retifanlimab.

• Nephrotoxicity: Retifanlimab can cause immune-mediated nephritis and kidney dysfunction. Grades 2, 3, and 4 events were observed. Approximately one-half of patients with immune-mediated nephritis required systemic corticosteroids, and approximately half of those experienced resolution. In the case where retifanlimab was withheld for nephritis, treatment was reinitiated after symptom improvement without nephritis recurrence.

• 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: Retifanlimab can cause immune-mediated pneumonitis. Immune-mediated pneumonitis was reported in a small percentage of patients, including grades 2 and 3 and a fatal event (case report). Most patients experiencing pneumonitis required management with systemic corticosteroids. Pneumonitis resolved in a majority of the affected patients. In cases where retifanlimab was withheld for pneumonitis, three-fourths of patients reinitiated retifanlimab after symptom improvement and there was one recurrence of pneumonitis. 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 retifanlimab (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, hypoparathyroidism, hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, and other transplant (including corneal graft) 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 allogeneic 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-a/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 IVIG 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.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Zynyz: Retifanlimab-dlwr 500 mg/20 mL (25 mg/mL) (20 mL) [contains polysorbate 80]

Generic Equivalent Available: US

Pricing: US

Solution (Zynyz Intravenous)

500 mg/20 mL (per mL): $884.58

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.

Administration: Adult

IV: Infuse over 30 minutes via a polyethylene, polyurethane, or PVC with di-2-ethylhexyl phthalate (DEHP) IV line containing a sterile, nonpyrogenic, low-protein-binding polyethersulfone, polyvinylidene fluoride, or cellulose acetate 0.2 to 5 micron inline or add-on filter or 15 micron mesh inline or add-on filter; do not administer using a polyurethane infusion set. Do not administer as IV push or bolus. Do not administer other medications through the same IV line. Monitor for signs/symptoms of infusion-related reactions. If an infusion reaction occurs, interrupt or slow the infusion rate or permanently discontinue retifanlimab based on severity of the reaction. Consider premedication with an antipyretic and/or an antihistamine for patients who have had previous systemic reactions to therapeutic protein infusions.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Zynyz (retifanlimab-dlwr): https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761334s004lbl.pdf#page=28

Use: Labeled Indications

Anal cancer, squamous cell carcinoma, locally recurrent or metastatic:

First-line treatment (in combination with carboplatin and paclitaxel) of inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal in adults.

Treatment (as a single agent) of locally recurrent or metastatic squamous cell carcinoma of the anal canal in adults with disease progression or intolerance to platinum-based chemotherapy.

Merkel cell carcinoma, metastatic or recurrent locally advanced: Treatment (as a single agent) of metastatic or recurrent locally advanced Merkel cell carcinoma in adults.

Medication Safety Issues

Sound-alike/look-alike issues:

Retifanlimab may be confused with cemiplimab, cosibelimab, dostarlimab, nivolumab/relatlimab, penpulimab, ramucirumab, rituximab, toripalimab.

Zynyz may be confused with Zynlonta, Zynteglo.

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Metabolism/Transport Effects

None known.

Drug Interactions

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 drug interactions program by clicking on the “Launch drug interactions program” link above.

Acetaminophen: May decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor

Antibiotics: May decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor

Corticosteroids (Systemic): May decrease therapeutic effects 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 decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor

Inhibitors of the Proton Pump (PPIs and PCABs): May decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor

Ketoconazole (Systemic): Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may increase hepatotoxic effects of Ketoconazole (Systemic). Risk C: Monitor

Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor

Opioid Agonists: Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may decrease therapeutic effects of Opioid Agonists. Opioid Agonists may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor

Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor

Vitamin K Antagonists: Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor

Reproductive Considerations

Verify pregnancy status prior to treatment initiation in patients who could become pregnant.

Patients who could become pregnant should use effective contraception during therapy and for 4 months after the last retifanlimab dose.

Endocrine-related adverse events during treatment with PD-1 immune checkpoint inhibitors may have direct or indirect effects on fertility, which may be reversible; however, human data are limited. Consider evaluating fertility status prior to treatment, the patient's desire for future pregnancies, and (if desired) options for fertility preservation (Garutti 2021; Hassel 2021; Lee 2025).

Pregnancy Considerations

Retifanlimab 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 gestational age, 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).

Animal reproduction studies have not been conducted. Based on the mechanism of action, in utero exposure to retifanlimab may disrupt maternal tolerance to the fetus, increasing the risk of abortion or stillbirth. Based on animal data, maternal use of a PD-1 inhibitor may also result in immune-mediated disorders in the newborn.

The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach (ESMO [Peccatori 2013]).

A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (877-635-4499).

Breastfeeding Considerations

It is not known if retifanlimab is present in human milk.

Retifanlimab 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 retifanlimab dose.

Monitoring Parameters

Monitor hepatic (ALT, AST, and total bilirubin; baseline and periodically during treatment) and kidney function (serum creatinine; baseline and periodically during treatment), 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.

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, ECG, 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.

Mechanism of Action

Retifanlimab is a humanized IgG₄ monoclonal antibody which is a programmed death receptor-1 (PD-1) blocking antibody. Retifanlimab binds to the PD-1 receptor, blocking interaction with its ligands, PD-L1 and PD-L2, and potentiating T-cell activity. PD-L1 and PD-L2 binding to the PD-1 receptor on T-cells inhibits T-cell proliferation and cytokine production. 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.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_dss: 6 L.

Half-life elimination: 19 days.

Excretion: Clearance: First dose: 0.3 L/day; Steady state: 0.23 L/day.

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Zynyz (retifanlimab) [prescribing information]. Wilmington, DE: Incyte Corporation; May 2025.

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