Retifanlimab-dlwr, a humanized anti-programmed-death receptor-1 (anti-PD-1) monoclonal antibody, is an antineoplastic agent.1
Squamous Cell Carcinoma of the Anal Canal
Retifanlimab-dlwr is used for the first-line treatment of adults with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal, in combination with carboplatin and paclitaxel.1 Retifanlimab-dlwr is also used as monotherapy in adults with locally recurrent or metastatic squamous cell carcinoma of the anal canal with disease progression on or intolerance to platinum-based chemotherapy.1 Retifanlimab-dlwr has been designated an orphan drug by FDA for treatment of anal cancer.2
Efficacy of retifanlimab-dlwr in combination with carboplatin and paclitaxel for squamous cell carcinoma of the anal canal was assessed in a randomized, multicenter, double-blind study (POD1UM-303).1, 7 Enrolled adults had inoperable locally recurrent or metastatic disease, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, received no prior systemic therapy, and had well-controlled HIV infection (if present).1, 7 A total of 308 patients were randomly assigned (1:1 ratio) to either retifanlimab-dlwr 500 mg IV every 4 weeks on Day 1, carboplatin AUC of 5 on Day 1, and paclitaxel 80 mg/m2 on Days 1, 8, and 15 for 6 cycles followed by retifanlimab-dlwr 500 mg IV every 4 weeks or the same dosage regimen of carboplatin and paclitaxel with placebo administered instead of retifanlimab-dlwr.1, 7 Treatment continued until disease progression, unacceptable toxicity, consent withdrawal, death, or up to 12 months.1, 7 The primary endpoint was progression-free survival, defined as time from randomization to date of initial documented disease progression or death from any cause.1, 7
The median age of enrolled patients was 62 (range: 29-86) years, 72% were female, and 87% were White, 6% Asian, and 1.6% Black.1 Most patients (55%) had an ECOG performance status of 0 and 83% had metastatic disease at baseline.1 Progression-free survival was significantly longer in the retifanlimab-dlwr plus carboplatin/paclitaxel group as compared to the carboplatin/paclitaxel only group (9.3 versus 7.4 months), with a median follow-up of 7.6 and 7.1 months, respectively.7 The overall response rate was also significantly improved with combination therapy involving retifanlimab-dlwr (55.8% versus 44.2%).7 In the retifanlimab-dlwr combination group, 22% had a complete response, 34% partial response, and 29% stable disease.7 This compared to a complete response rate of 14%, partial response of 31%, and stable disease response of 34% in the carboplatin/paclitaxel only group.7
Efficacy of retifanlimab-dlwr as monotherapy for squamous cell carcinoma of the anal canal was assessed in an open-label, multicenter, single-arm study (POD1UM-202).1, 8 Enrolled adults had locally advanced or metastatic disease with progression on or after platinum-based therapy, an ECOG performance status of 0 or 1, and had well-controlled HIV infection (if present).1, 8 A total of 94 patients were administered retifanlimab-dlwr 500 mg IV every 4 weeks until disease progression, unacceptable toxicity, or up to 24 months.1, 8 The primary endpoint was overall response rate.1, 8
The median age of enrolled patients was 64 (range: 37-94) years, 65% were female, and 77% were White and 1.1% Black.1 Most patients (59%) had an ECOG performance status of 1 and 81% had metastatic disease at baseline.1 The overall response rate was 13.8% with a median duration of follow-up of 7.1 months.8 A single patient (1.1%) had a complete response and 12 patients (12.8%) had a partial response; an additional 33 patients (35.1%) experienced stable disease.8
Retifanlimab-dlwr is used for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC).1 Retifanlimab-dlwr has been designated an orphan drug by FDA for use in the treatment of MCC.2
Efficacy of retifanlimab-dlwr for adults with MCC was assessed in an open-label, phase 2, single-arm study (POD1UM-201).1, 3 Enrolled patients had metastatic or recurrent locally advanced MCC with no prior systemic therapy for advanced disease and an ECOG performance status ≤1.1, 3 All patients received retifanlimab-dlwr 500 mg IV every 4 weeks for up to 24 months or until disease progression or unacceptable toxicity.1 The primary endpoint was overall response rate; duration of response was assessed as a secondary outcome.1, 3
A total of 101 patients were enrolled in the trial; the median age was 71 (range: 38-90) years, 67% were male, and 77% were White.1 Most patients (73%) had an ECOG performance status of 0, and 90% had metastatic disease at baseline.1 The overall response rate was 55%, with 18% of patients demonstrating a complete response and 37% with a partial response.1 Duration of response ranged from 1.1 to beyond 55.3 months; 69% of patients had response durations of ≥12 months and 46% of patients had response durations of ≥24 months.1
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer, with 5-year survival rates ranging from 51% for local disease to 14% for metastatic disease.4, 5 Treatment recommendations for MCC are primarily based on case series, with limited data from clinical trials; treatment selection is highly individualized based on the specifics of the case as well as institutional, provider, and patient preference.6 Surgical excision of the primary lesion, regional lymph node dissection, and adjuvant radiation therapy are commonly employed to treat localized MCC.5, 6 A variety of chemotherapy regimens have historically been used to treat advanced or recurrent disease.5, 6 Immunotherapy has emerged as a first-line treatment option in patients with locally advanced or metastatic MCC; this typically involves the use of an anti-programmed death receptor-1 (PD-1) antibody (e.g., pembrolizumab, retifanlimab, nivolumab) or anti-programmed death ligand-1 (PD-L1) antibody (e.g., avelumab).4, 5, 6
Retifanlimab-dlwr is administered by IV infusion.1 It is available as a solution containing 500 mg/20 mL (25 mg/mL) in a single-dose vial.1
Store unopened vials in the refrigerator at 2-8ºC; do not freeze or shake.1 Store in the original carton to protect from light.1
Dilute retifanlimab-dlwr injection prior to IV administration.1
Administer the diluted solution through a polyethylene, polyurethane, or polyvinylchloride (PVC) and di-2-ethylhexyl phthalate (DEHP) IV line containing a sterile, non-pyrogenic, low-protein binding polyethersulfone, polyvinylidene fluoride, or cellulose acetate 0.2-5 micron in-line or add-on filter, or 15 micron mesh in-line or add-on filter.1 Do not coadminister other drugs through the same infusion line.1
Visually inspect vials for particulate matter and discoloration; retifanlimab-dlwr is a clear to slightly opalescent, colorless to pale yellow solution that is free of particles.1 Discard the vial if the solution is cloudy, discolored, or contains particulate matter.1 Do not shake the vial.1
To prepare the diluted solution, withdraw 20 mL of retifanlimab-dlwr for the 500 mg dose and 15 mL of retifanlimab-dlwr for the 375 mg dose.1 Discard any unused portion.1
Dilute retifanlimab-dlwr with either 0.9% sodium chloride injection or 5% dextrose injection to a final concentration of 1.4-10 mg/mL.1 Use PVC with DEHP, polyolefin copolymer, polyolefin with polyamide, or ethylene vinyl acetate infusion bags.1
Mix the diluted solution by gentle inversion; do not shake.1 Visually inspect the infusion bag for particulate matter and discoloration prior to administration; discard the solution if discoloration or visible particulates are observed.1
Protect the diluted solution from light during storage.1 Store the diluted solution at room temperature (up to 25ºC) for no more than 8 hours from the time of preparation to the end of infusion, or refrigerated (2-8ºC) for no more than 24 hours from the time of preparation to the end of infusion.1 Allow the refrigerated diluted solution to come to room temperature prior to administration; administer the diluted solution within 4 hours (including infusion time) once it is removed from the refrigerator.1 Do not freeze or shake the diluted solution.1
Administer the diluted solution by IV infusion over 30 minutes.1 Do not administer retifanlimab-dlwr as an IV push or bolus injection.1
Squamous Cell Carcinoma of the Anal Canal
For the treatment of adults with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal in combination with carboplatin and paclitaxel, the recommended dosage of retifanlimab-dwlr is 500 mg given as an IV infusion over 30 minutes every 4 weeks or 375 mg given as an IV infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 12 months.1 Clinicians should refer to the prescribing information for medications administered with retifanlimab-dwlr for recommended dosage information.1
For the treatment of adults with locally recurrent or metastatic squamous cell carcinoma of the anal canal with disease progression on or intolerance to platinum-based chemotherapy, the recommended dosage of retifanlimab-dwlr monotherapy is 500 mg as an IV infusion over 30 minutes every 4 weeks or 375 mg as an IV infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.1
For the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma, the recommended dosage of retifanlimab-dlwr monotherapy is 500 mg given as an IV infusion over 30 minutes every 4 weeks until disease progression, unacceptable toxicity, or up to 24 months.1
Dosage Modification for Adverse Reactions
If adverse reactions occur, dosage reductions of retifanlimab-dlwr are not recommended.1
Generally, withhold retifanlimab-dlwr for severe (grade 3) immune-mediated adverse reactions.1 Permanently discontinue retifanlimab-dlwr for life-threatening (grade 4) immune-mediated adverse reactions and recurrent severe (grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or if unable to reduce corticosteroid dose to ≤10 mg of prednisone equivalent per day within 12 weeks of steroid initiation.1
Dosage modifications for adverse reactions that require different management from the general guidelines stated above are outlined in Table 1.1
Adverse Reaction | Dosage Modification Based on Severity |
|---|---|
Pneumonitis | Grade 2: Withholda Grade 3 or 4: Permanently discontinue |
Colitis | Grade 2 or 3: Withholda Grade 4: Permanently discontinue |
Hepatitis without tumor involvement of the liver | AST or ALT >3 but ≤8 times ULN OR total bilirubin increases to >1.5 and ≤3 times ULN: Withholda AST or ALT increases to >8 times ULN OR total bilirubin >3 times ULN: Permanently discontinue |
Hepatitis with tumor involvement of the liver | Baseline AST and ALT are ≤ULN: Withhold or permanently discontinue based on recommendations for hepatitis without tumor involvement of the liver Baseline AST or ALT is >1 and ≤3 times ULN and increases >5 and ≤10 times ULN OR Baseline AST or ALT is >3 and ≤5 times ULN and increases >8 and ≤10 times ULN: Withholda AST or ALT increases to >10 times ULN OR total bilirubin increases to >3 times ULN: Permanently discontinue |
Endocrinopathies | Grade 2: Depending on clinical severity, consider withholding until symptom improvement with hormone replacement; resume once acute symptoms have resolved Grade 3 or 4: Withhold until clinically stable or permanently discontinue depending on severity |
Nephritis with renal dysfunction | Grade 2 or 3 increased blood creatinine: Withholda Grade 4 increased blood creatinine: Permanently discontinue |
Exfoliative dermatologic conditions | Grade 3 or suspected Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug rash with eosinophilia and systemic symptoms (DRESS): Withholda Grade 4 or confirmed Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS: Permanently discontinue |
Myocarditis | Grade 2, 3, or 4: Permanently discontinue |
Neurological toxicities | Grade 2: Withholda Grade 3 or 4: Permanently discontinue |
Infusion-related reactions | Grade 1 or 2: Interrupt or slow the rate of infusion Grade 3 or 4: Permanently discontinue |
aResume in patients with complete or partial resolution (grade 0 to 1) after corticosteroid taper. Permanently discontinue if no resolution within 12 weeks of steroid initiation or inability to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of steroid initiation.
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Immune-mediated Adverse Reactions
Retifanlimab-dlwr removes inhibition of the immune response; this may break peripheral tolerance and induce immune-mediated adverse reactions.1 Severe and fatal immune-mediated adverse reactions may occur in any organ system or tissue; reactions affecting more than 1 body system can occur simultaneously.1 Immune-mediated reactions may occur at any time after retifanlimab-dlwr initiation.1 Reactions generally occur during treatment but may also occur after the drug is discontinued.1
Early identification and management of immune-mediated adverse reactions are necessary to ensure safe use of retifanlimab-dlwr.1 Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions.1 Assess liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.1 If suspected immune-mediated reactions occur, initiate appropriate workup to exclude alternative causes (including infection).1 Medically manage immune-mediated adverse reactions promptly and refer for specialty consultation as appropriate.1
Withhold or permanently discontinue retifanlimab-dlwr depending on the nature and severity of the reaction.1 If retifanlimab-dlwr treatment interruption or discontinuation is required, administer systemic corticosteroids (1-2 mg/kg per day prednisone or equivalent) until improvement to grade 1 or less, then initiate corticosteroid taper and continue to taper over ≥1 month.1 Consider administration of other systemic immunosuppressants if the reaction is not controlled with corticosteroid therapy.1
The immune-mediated adverse reactions described in the following sections may not be inclusive of all possible severe and fatal immune-mediated reactions.1 Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies, dermatologic reactions) are discussed below.1
Retifanlimab-dlwr may cause immune-mediated pneumonitis.1 In patients treated with other programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) blocking monoclonal antibodies, the incidence of pneumonitis is higher in patients with a history of prior thoracic radiation.1
Immune-mediated pneumonitis was reported in 3.1% of patients receiving retifanlimab-dlwr; grade 2 and 3 events occurred in 1.3 and 0.9% of patients, respectively, and 1 patient experienced fatal pneumonitis.1 Most patients (71%) required management with systemic corticosteroids.1 Pneumonitis resolved in 11 of the 14 affected patients.1 Five patients had retifanlimab-dlwr withheld for pneumonitis; of these, 4 patients reinitiated therapy after symptom improvement, and 1 patient experienced recurrence of pneumonitis.1
Retifanlimab-dlwr may cause immune-mediated colitis.1 Cytomegalovirus infection/reactivation has occurred in patients with corticosteroid-refractory immune-mediated colitis who were treated with anti-PD-1/PD-L1 monoclonal antibodies.1 In patients with corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.1
Immune-mediated colitis has been reported in 2.7% of patients treated with retifanlimab-dlwr monotherapy; grade 2, 3, and 4 events were reported in 1.1, 0.4, and 0.2% of patients, respectively.1 Systemic corticosteroids were required for management in 75% of patients.1 Colitis resolved in 8 of 12 patients.1 Of the 6 patients in whom retifanlimab-dlwr was withheld for colitis, 1 reinitiated treatment after symptom improvement and did not experience recurrence.1
Immune-mediated colitis has been reported in 10% of patients treated with retifanlimab-dlwr in combination with carboplatin and paclitaxel; grade 2, 3, and 4 events were reported in 3.2, 2.6, and 0.6% of patients, respectively.1 Systemic corticosteroids were required for management in 94% of patients.1 Colitis resolved in 15 of 16 patients.1 Of the 2 patients in whom retifanlimab-dlwr was withheld for colitis, both reinitiated treatment after symptom improvement and did not experience recurrence.1
Retifanlimab-dlwr can cause immune-mediated hepatitis.1
Immune-mediated hepatitis was reported in 3.5% of patients receiving retifanlimab-dlwr; grade 2, 3, and 4 events were reported in 0.9, 2.4, and 0.2% of patients, respectively.1 Systemic corticosteroids were required in 81% of patients.1 Hepatitis resolved in 9 of 16 patients.1 Of the 5 patients in whom retifanlimab-dlwr was withheld for hepatitis, 3 patients reinitiated treatment after symptom improvement; 1 of these patients experienced recurrence of hepatitis.1
Immune-mediated endocrinopathies, including adrenal insufficiency, hypophysitis, thyroid dysfunction (i.e., hyperthyroidism, hypothyroidism, thyroiditis), and type 1 diabetes, have occurred in patients receiving retifanlimab-dlwr therapy.1
Retifanlimab-dlwr can cause primary and secondary adrenal insufficiency.1 Grade 2 and 3 events have been reported in patients who were administered monotherapy (0.4% for each); in patients given combination therapy with carboplatin and paclitaxel, these events have also been reported (1.9% for each).1 Adrenal insufficiency did not lead to permanent discontinuation of retifanlimab-dlwr in any patient on monotherapy; however, a single patient administered combination therapy discontinued retifanlimab-dwlr.1 All patients required systemic corticosteroids.1 If grade 2 or higher adrenal insufficiency occurs, initiate symptomatic treatment per institutional guidelines, including hormone replacement therapy as clinically indicated.1 Withhold or permanently discontinue retifanlimab-dlwr depending on severity.1
Retifanlimab-dlwr can cause immune-mediated hypophysitis, which may present with acute symptoms associated with mass effect (e.g., headache, photophobia, visual field cuts).1 Hypophysitis may lead to hypopituitarism.1 Three cases of hypophysitis have been reported in patients receiving retifanlimab-dlwr.1 All cases required systemic corticosteroids; hypophysitis resolved in 1 of the cases.1 If hypophysitis occurs, initiate hormone replacement therapy as clinically indicated.1 Withhold or permanently discontinue retifanlimab-dlwr depending on severity.1
Retifanlimab-dlwr can cause immune-mediated thyroid disorders, including thyroiditis, hyperthyroidism, and hypothyroidism.1 Thyroiditis may present with or without endocrinopathy.1 Hypothyroidism may follow hyperthyroidism.1 Grade 1 thyroiditis has been reported in 0.7% of patients receiving retifanlimab-dlwr.1 Cases of thyroiditis did not require treatment interruption or discontinuation, and thyroiditis resolved in 1 of 3 reported cases.1 Hyperthyroidism has been reported in 6% of patients receiving retifanlimab-dlwr, with grade 2 events occurring in 2.7% of patients.1 Systemic corticosteroids were required in 15% of patients with hyperthyroidism, and endocrine therapy was required in 50% of patients.1 Hypothyroidism has been reported in 10% of patients receiving retifanlimab-dlwr, with grade 2 events occurring in 4.9% of patients.1 While 0.4% of patients required treatment interruption due to hypothyroidism, no patients required permanent discontinuation; 1 patient required systemic corticosteroids and 78% required endocrine therapy.1 If an immune-mediated thyroid disorder occurs, initiate hormone replacement therapy or medical management of hyperthyroidism as clinically indicated.1 Withhold or permanently discontinue retifanlimab-dlwr depending on severity.1
Type 1 diabetes has been reported in 1 patient receiving retifanlimab-dlwr, leading to treatment interruption and administration of insulin.1 Monitor patients for hyperglycemia or other signs and symptoms of diabetes.1 Initiate insulin therapy as clinically indicated.1 Withhold retifanlimab-dlwr depending on severity.1
Nephritis with Renal Dysfunction
Immune-mediated nephritis has been reported in 2% of patients receiving retifanlimab-dlwr.1 Grade 2, 3, and 4 events have been reported in 0.4, 1.1, and 0.4% of patients, respectively.1 Six of 9 patients with immune-mediated nephritis required systemic corticosteroids.1 Four of the 9 patients experienced nephritis resolution.1 In the 3 cases where retifanlimab-dlwr was withheld for nephritis, treatment was reinitiated after symptom improvement without recurrence of nephritis in 1 patient.1
Dermatologic Adverse Reactions
Retifanlimab-dlwr may cause immune-mediated rash or dermatitis.1 Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), has occurred with anti-PD-1/PD-L1 monoclonal antibodies.1
Immune-mediated skin reactions occurred in 10% of patients receiving retifanlimab-dlwr; reactions were grade 2, 3, and 4 events in 8, 1.1, and 0.2% of patients, respectively.1 Immune-mediated dermatologic reactions were treated with systemic corticosteroids in 33% of patients.1 Reactions resolved in 72% of patients.1 Of the 12 patients in whom retifanlimab-dlwr was withheld for dermatologic toxicity, 8 reinitiated treatment after symptom improvement; two of these patients experienced recurrence of immune-mediated dermatologic toxicity.1
For treatment of mild to moderate non-exfoliative rashes, topical emollients and/or topical corticosteroids may be adequate.1 Withhold or permanently discontinue retifanlimab-dlwr depending on severity.1
Other Immune-mediated Adverse Reactions
Other clinically important immune-mediated adverse reactions have been observed rarely with retifanlimab-dlwr (or other anti-PD-1/PD-L1 monoclonal antibodies); in some instances, these reactions were severe or fatal.1
Specific reactions have included cardiac/vascular disorders (myocarditis, pericarditis, vasculitis); GI disorders (pancreatitis, gastritis, duodenitis); musculoskeletal disorders (myositis/polymyositis, rhabdomyolysis and associated sequelae, arthritis, polymyalgia rheumatica); neurologic disorders (meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis [including exacerbation], Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy); hypoparathyroidism; ocular disorders (uveitis, iritis, other ocular inflammatory toxicities); and other hematologic/immune disorders (hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis [Kikuchi lymphadenitis], sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant [including corneal graft] rejection).1
Some cases of ocular toxicity may be associated with retinal detachment.1 Various grades of visual impairment (including blindness) can occur.1 If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome.1
A severe (grade 3) infusion-related reaction was reported in 5 patients in retifanlimab-dlwr clinical trials.1
Monitor patients for signs and symptoms of infusion-related reactions.1 Slow the rate of infusion, interrupt the infusion, or permanently discontinue retifanlimab-dlwr based on the severity of the reaction.1
Consider premedication with an antipyretic, antihistamine, or both in patients who have had previous systemic reactions to infusions of therapeutic proteins.1
Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Serious or fatal complications can occur in patients who receive allogeneic HSCT before or after treatment with an anti-PD-1/PD-L1 antibody.1 Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome without an identified infectious cause.1 Complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT.1
Closely monitor patients for evidence of transplant-related complications and intervene promptly.1 Weigh the benefits versus risks of retifanlimab-dlwr therapy prior to or after an allogeneic HSCT.1
Fetal/Neonatal Morbidity and Mortality
Retifanlimab-dlwr may cause fetal harm if administered to a pregnant woman based on its mechanism of action and findings from animal studies.1 Inhibition of the PD-1/PD-L1 pathway in animals has been shown to increase the risk of immune-mediated rejection of the developing fetus, resulting in fetal death.1
Perform pregnancy testing in females of reproductive potential prior to initiating retifanlimab-dlwr.1 Advise pregnant women of the potential risk to a fetus.1 Advise females of reproductive potential to use effective contraception during treatment with retifanlimab-dlwr and for 4 months after the last dose.1
There is potential for immunogenicity with retifanlimab-dlwr therapy.1
Retifanlimab treatment-emergent anti-drug antibodies were detected in 3 patients (2.8%) with MCC using a bridging enzyme-linked immunosorbent assay following a median exposure time of 312 days.1 Neutralizing antibodies to retifanlimab-dlwr were detected in 2 of 3 patients with treatment-emergent anti-drug antibodies.1 The effects of these antibodies on the safety, efficacy, pharmacokinetics, and/or pharmacodynamics of retifanlimab products are unknown.1
None of the patients in clinical trials of retifanlimab-dlwr for squamous cell carcinoma of the anal canal tested positive for treatment-emergent anti-drug antibodies.1
Retifanlimab-dlwr may cause fetal harm if administered to a pregnant woman based on its mechanism of action and findings from animal reproduction studies.1 There are no available human data on retifanlimab-dlwr use during pregnancy.1 In animals, inhibition of the PD-1/PD-L1 pathway has been shown to increase the risk of immune-mediated rejection of the developing fetus, resulting in fetal death.1
Since human immunoglobulin G4 (IgG4) is known to cross the placenta, retifanlimab-dlwr has the potential to be transmitted from the mother to the developing fetus.1
Perform pregnancy testing in females of reproductive potential prior to initiating retifanlimab-dlwr.1 Advise pregnant women of the potential risk to a fetus.1
It is unknown whether retifanlimab-dlwr distributes into human milk; effects on milk production or the breast-fed infant are also unknown.1 Maternal immunoglobulin G (IgG) is known to be distributed into human milk.1 The effects of local GI exposure and limited systemic exposure to retifanlimab-dlwr in the breast-fed infant are unknown.1
Because of the potential for serious adverse reactions in breast-fed infants, advise women to not breast-feed during treatment with retifanlimab-dlwr and for 4 months after the last dose.1
Females and Males of Reproductive Potential
Perform pregnancy testing in females of reproductive potential prior to initiating retifanlimab-dlwr.1
Advise females of reproductive potential to use effective contraception during treatment with retifanlimab-dlwr and for 4 months after the last dose.1
Safety and efficacy of retifanlimab-dlwr have not been established in pediatric patients.1
Of the 154 patients with metastatic squamous cell carcinoma of the anal canal treated with retifanlimab-dlwr in combination with carboplatin and paclitaxel, 38 and 9% were ≥65 years and ≥75 years of age, respectively.1 No overall differences in the efficacy or safety of retifanlimab-dlwr were observed in younger and older patients.1
Of the 94 patients with locally recurrent or metastatic squamous cell carcinoma of the anal canal treated with retifanlimab-dlwr monotherapy, 49 and 11% were ≥65 years and ≥75 years of age, respectively.1
Of the 101 patients with metastatic or recurrent locally advanced Merkel cell carcinoma treated with retifanlimab-dlwr monotherapy, 76 and 39% were ≥65 years and ≥75 years of age, respectively.1
Clinical studies evaluating retifanlimab-dlwr as monotherapy did not include sufficient numbers of younger adults to determine whether geriatric patients respond differently than younger adults.1
No clinically important differences in retifanlimab-dlwr pharmacokinetics were observed based on age (range, 18-94 years).1
No clinically important differences in retifanlimab-dlwr pharmacokinetics were observed in patients with mild (Child-Pugh A) hepatic impairment (total bilirubin less than or equal to the upper limit of normal [ULN] and AST greater than ULN, or total bilirubin greater than ULN and ≤1.5 times ULN with any AST).1 The pharmacokinetics of retifanlimab-dlwr have not been studied in patients with moderate (Child-Pugh B) or severe hepatic impairment (Child-Pugh C).1
No clinically important effects on retifanlimab-dlwr pharmacokinetics were observed based on renal function (estimated glomerular filtration rate [eGFR] ≥26 mL/minute per 1.73 m2).1
Adverse effects reported in ≥10% of patients receiving retifanlimab-dlwr for MCC include fatigue, musculoskeletal pain, pruritus, diarrhea, rash, pyrexia, nausea, and constipation.1
Adverse effects reported in ≥10% of patients receiving retifanlimab-dlwr monotherapy for squamous cell carcinoma of the anal canal include fatigue, musculoskeletal pain, diarrhea, non-urinary tract infections, perineal pain, hemorrhage, urinary tract infection, rash, nausea, decreased appetite, constipation, abdominal pain, dyspnea, pyrexia, vomiting, cough, pruritus, hypothyroidism, headache, and decreased weight.1
Adverse effects reported in ≥20% of patients receiving retifanlimab-dlwr in combination therapy for squamous cell carcinoma of the anal canal include fatigue, peripheral neuropathy, nausea, alopecia, diarrhea, musculoskeletal pain, constipation, hemorrhage, rash, vomiting, decreased appetite, pruritus, and abdominal pain.1
Retifanlimab is a humanized immunoglobulin G4 (IgG4) kappa monoclonal antibody that blocks programmed death receptor-1 (PD-1).1 It is produced in Chinese hamster ovary cells.1 Retifanlimab binds to the PD-1 receptor, blocking its interaction with programmed death ligand (PD-L) 1 and PD-L2, potentiating T-cell activity.1 Binding of PD-L1 and PD-L2 to the PD-1 receptor on T cells inhibits T-cell proliferation and cytokine production.1 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.1
The exposure-response relationship and time course of pharmacodynamic response of retifanlimab-dlwr have not been fully characterized.1 Retifanlimab-dlwr pharmacokinetics were assessed in patients with various solid tumors, including patients with Merkel cell carcinoma and squamous cell carcinoma of the anal canal.1 Retifanlimab-dlwr peak plasma concentrations and AUC increased proportionally over the dose range of 375-750 mg.1 Steady-state concentrations were achieved by approximately 3 months following repeated administration of retifanlimab-dlwr; systemic accumulation was 1.3-fold.1 The elimination half-life of retifanlimab-dlwr at steady state is 19 days.1
No clinically important differences in retifanlimab-dlwr pharmacokinetics were observed based on age (18-94 years), sex, body weight (33-133 kg), race (white, Black, Asian), albumin level (17-54 g/L), Eastern Cooperative Oncology Group score (0 to 2), tumor burden (sum of the target lesion diameters, 0-360 mm), HIV status, renal function (estimated glomerular filtration rate ≥26 mL/minute per 1.73 m2), or mild hepatic impairment (total bilirubin ≤ the upper limit of normal [ULN] and AST greater than ULN, or total bilirubin greater than ULN and ≤1.5 times ULN with any AST).1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection concentrate, for IV infusion | 25 mg/mL | Zynyz® | Incyte |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions August 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Incyte Corporation. Zynyz® (retifanlimab-dlwr) INTRAVENOUS prescribing information. Wilmington, DE; 2026 May.
2. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. [Web]
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