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ZYNYZ is a brand name for Retifanlimab. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE ZYNYZ is a programmed death receptor-1 (PD-1)–blocking antibody indicated: Squamous Cell Carcinoma of the Anal Canal (SCAC) in combination with carboplatin and paclitaxel for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of…
Verbatim from this product's FDA label. Tap a section to expand.
2 ) and preparation and administration instructions. 1 Recommended Dosage The recommended dosages of ZYNYZ are provided in Table 1. 3 )] .
Table 1:
Recommended Dosage of ZYNYZ Indication Recommended Dosage of ZYNYZ Duration of Treatment Combination Therapy Refer to the Prescribing Information for the agents administered in combination with ZYNYZ for recommended dosing information, as appropriate.
2 Dosage Modifications for Adverse Reactions No dose reduction of ZYNYZ is recommended. In general, withhold ZYNYZ for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue ZYNYZ for life‑threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids.
Dosage modifications for ZYNYZ for adverse reactions that require management different from these general guidelines are summarized in Table 2.
Table 2:
Recommended Dosage Modifications for Adverse Reactions AST = aspartate aminotransferase; ALT = alanine aminotransferase; DRESS = drug rash with eosinophilia and systemic symptoms; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; ULN = upper limit of normal.
Adverse Reaction Severity Toxicity graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5. 1 )] Pneumonitis Grade 2 Withhold Resume in patients with complete or partial resolution (Grade 0-1) after corticosteroid taper.
Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids. 5 and up to 3 times ULN Withhold AST or ALT increases to more than 8 times ULN OR Total bilirubin greater than 3 times ULN Permanently discontinue Hepatitis with tumor involvement of the liver If AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue ZYNYZ based on recommendations for hepatitis with no liver involvement.
6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in the labeling. 3 )] ZYNYZ in Combination with Carboplatin and Paclitaxel In patients with SCAC, the most common (≥ 20%) adverse reactions are fatigue, peripheral neuropathy, nausea, alopecia, diarrhea, musculoskeletal pain, constipation, hemorrhage, rash, vomiting, decreased appetite, pruritus, and abdominal pain.
1 ) ZYNYZ as a Single Agent In patients with SCAC, the most common (≥ 10%) adverse reactions are 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 ) In patients with MCC, the most common (≥ 10%) adverse reactions are musculoskeletal pain, fatigue, pruritus, diarrhea, rash, pyrexia, nausea, and constipation. gov/medwatch . 1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety population described in Warnings and Precautions reflects exposure to ZYNYZ 500 mg as an intravenous infusion every 4 weeks in combination with carboplatin and paclitaxel in 154 patients with SCAC enrolled in the POD1UM-303 trial, and as a single agent in 94 patients with SCAC in the POD1UM-202 trial, 107 patients with MCC in the POD1UM-201 trial, and 251 patients with other solid tumors.
All patients received ZYNYZ until disease progression or unacceptable toxicity; those in the POD1UM-202 and POD1UM-201 trials received ZYNYZ for up to 24 months and those in the POD1UM-303 trial received ZYNYZ for up to 12 months. 4 months (range: 1 day to 27 months).
1 ) Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune‑mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis with renal dysfunction, and immune‑mediated dermatologic adverse reactions, and solid organ transplant rejection.
Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. Withhold or permanently discontinue ZYNYZ and administer corticosteroids based on the severity of reaction.
2 ) Infusion-Related Reactions: Interrupt, slow the rate of infusion, or permanently discontinue ZYNYZ based on severity of reaction. 2 ) Complications of Allogeneic HSCT: Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD‑1/PD‑L1–blocking antibody.
3 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception. 1 Severe and Fatal Immune-Mediated Adverse Reactions ZYNYZ is a monoclonal antibody that belongs to a class of drugs that binds to either the programmed death receptor-1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response with the potential for breaking of peripheral tolerance and induction of immune-mediated adverse reactions.
Important immune‑mediated adverse reactions listed under Warnings and Precautions may not be inclusive of all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue.
Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1–blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1–blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1–blocking antibodies.
4 CONTRAINDICATIONS None. None. ( 4 )
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Baseline AST or ALT is more than 1 and up to 3 times ULN and increases more than 5 and up to 10 times ULN OR Baseline AST or ALT is more than 3 and up to 5 times ULN and increases more than 8 and up to 10 times ULN Withhold AST or ALT increases to more than 10 times ULN OR Total bilirubin increases to more than 3 times ULN Permanently discontinue Endocrinopathies Depending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with hormone replacement.
Resume once acute symptoms have resolved. 3 Preparation and Administration Visually inspect the vial for particulate matter and discoloration prior to administration. ZYNYZ is a clear to slightly opalescent, colorless to pale yellow solution and is free of particles.
Discard the vial if the solution is cloudy, discolored, or contains particulate matter. Do not shake the vial. Preparation Withdraw the appropriate volume from a vial of ZYNYZ: 20 mL for the 500 mg dose 15 mL for the 375 mg dose Discard the vial with any unused portion.
Each vial is for one-time use in only one patient. 4 mg/mL and 10 mg/mL. Use polyvinylchloride (PVC) and di-2-ethylhexyl phthalate (DEHP), polyolefin copolymer, polyolefin with polyamide, or ethylene vinyl acetate infusion bags. Mix diluted solution by gentle inversion.
Do not shake. Visually inspect the infusion bag for particulate matter and discoloration prior to administration. Discard if the solution is discolored or contains particulate matter. Storage of diluted ZYNYZ solution Protect the diluted ZYNYZ solution from light during storage.
Store diluted ZYNYZ solution:
At room temperature [up to 25°C (77°F)] for no more than 8 hours from the time of preparation to the end of the infusion. OR Under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 24 hours from the time of preparation to the end of the infusion.
If refrigerated, allow the diluted solution to come to room temperature prior to administration. The diluted solution must be administered within 4 hours (including infusion time) once it is removed from the refrigerator. Do not freeze or shake diluted solution.
2 micron to 5 micron in-line or add-on filter or 15 micron mesh in-line or add-on filter. Do NOT administer ZYNYZ as an intravenous push or bolus injection. Do not co‑administer other drugs through the same infusion line.
1 )] . Patients received ZYNYZ 500 mg or placebo intravenously every 4 weeks in combination with carboplatin and paclitaxel for 6 cycles followed by ZYNYZ 500 mg or placebo every 4 weeks until disease progression or unacceptable toxicity.
6 months). Serious adverse reactions occurred in 47% of patients receiving ZYNYZ in combination with carboplatin and paclitaxel. 6%). In patients receiving ZYNYZ in combination with carboplatin and paclitaxel, ZYNYZ was permanently discontinued due to an adverse reaction in 11% of patients.
Adverse reactions that resulted in permanent discontinuation of ZYNYZ included immune-mediated enterocolitis (2 patients), warm autoimmune hemolytic anemia, hepatitis, adrenal insufficiency, blood bilirubin increased, AST increased, blood alkaline phosphatase increased, arthritis, encephalopathy, peripheral sensorimotor neuropathy, hypothyroidism, immune‑mediated cholangitis, pruritus, malaise, and rash (1 patient each).
Dosage interruptions due to an adverse reaction, excluding temporary interruptions due to infusion-related reactions, occurred in 55% of patients who received ZYNYZ in combination with carboplatin and paclitaxel. Adverse reactions that resulted in dosage interruptions in ≥ 2% of patients were neutropenia, anemia, thrombocytopenia, leukopenia, fatigue, COVID-19, and urinary tract infection.
The most common (≥ 20%) adverse reactions were fatigue, peripheral neuropathy, nausea, alopecia, diarrhea, musculoskeletal pain, constipation, hemorrhage, rash, vomiting, decreased appetite, pruritus, and abdominal pain. Table 3 and Table 4 summarize adverse reactions and laboratory abnormalities, respectively, that occurred in POD1UM-303.
Table 3:
Adverse Reactions in ≥ 10% of Patients with Inoperable Locally Recurrent or Metastatic SCAC Receiving ZYNYZ in Combination with Carboplatin and Paclitaxel with a Difference Between Arms of ≥ 5% for All Grades or ≥ 2% for Grades 3 or 4 vs Placebo in Combination with Carboplatin and Paclitaxel in POD1UM-303 ZYNYZ in Combination with Carboplatin and Paclitaxel (N = 154) Placebo in Combination with Carboplatin and Paclitaxel (N = 152) Adverse Reaction All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%) Gastrointestinal disorders Diarrhea Includes diarrhea, colitis, and frequent bowel movements.
49 5 41 7 Stomatitis Includes stomatitis, aphthous ulcer, cheilitis, mouth ulceration, and mucosal inflammation. 18 0 11 0 Nervous system disorders Peripheral neuropathy Includes peripheral neuropathy, paresthesia, peripheral sensory neuropathy, neuralgia, hypoesthesia, peripheral sensorimotor neuropathy, dysesthesia, peripheral motor neuropathy, and hyperesthesia.
6 Musculoskeletal and connective tissue disorders Musculoskeletal pain Includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal stiffness, myalgia, neck pain, non-cardiac chest pain, pain in extremity, and spinal pain.
6 34 0 Vascular disorders Hemorrhage Includes hemorrhage, anal hemorrhage, anal ulcer hemorrhage, conjunctival hemorrhage, epistaxis, gastrointestinal hemorrhage, genital hemorrhage, hematuria, hemoptysis, hemorrhoidal hemorrhage, lower gastrointestinal hemorrhage, lymph node hemorrhage, rectal hemorrhage, stoma site hemorrhage, tumor hemorrhage, urinary bladder hemorrhage, uterine hemorrhage, vaginal hemorrhage, and wound hemorrhage.
2 21 0 Skin and subcutaneous tissue disorders Rash Includes rash, eczema, dermatitis acneiform, dermatitis, rash erythematous, rash maculo-papular, rash papular, rash pustular, and rash pruritic. 0.
Table 4:
Laboratory Abnormalities that Worsened from Baseline to Grade 3 or 4 Occurring in ≥ 1% of Patients with Inoperable Locally Recurrent or Metastatic SCAC Receiving ZYNYZ in Combination with Carboplatin and Paclitaxel in POD1UM-303 ZYNYZ in Combination with Carboplatin and Paclitaxel The denominator used to calculate the rate varied from 142 to 153 based on the number of patients with a baseline value and at least one post-treatment value.
0. 1 )] . Patients received ZYNYZ 500 mg intravenously every 4 weeks until disease progression, unacceptable toxicity, or up to 24 months. 1 months). Serious adverse reactions occurred in 40% of patients receiving ZYNYZ. The most frequent serious adverse reactions (≥ 2% of patients) were non-urinary tract infection, perineal pain, abdominal pain, anemia, hemorrhage, diarrhea, pyrexia, urinary tract infection, musculoskeletal pain, and dyspnea.
3% of patients. These adverse reactions included diarrhea, non-urinary tract infection, perineal pain, and rash. Dosage interruptions due to an adverse reaction occurred in 21% of patients who received ZYNYZ. Adverse reactions that resulted in dose delay in ≥ 2% of patients who received ZYNYZ were non-urinary tract infection, rash, diarrhea, abdominal pain, hemorrhage, musculoskeletal pain, pyrexia, and urinary tract infection.
The most common (≥ 10%) adverse reactions that occurred in patients receiving ZYNYZ were 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.
Table 5 and Table 6 summarize adverse reactions and laboratory abnormalities, respectively, that occurred in POD1UM-202.
Table 5:
Adverse Reactions in ≥ 10% of Patients with Platinum-Refractory Locally Recurrent or Metastatic SCAC Receiving ZYNYZ in POD1UM-202 Adverse Reaction ZYNYZ (N = 94) All Grades (%) Grades 3-4 (%) General disorders and administration site conditions Fatigue Includes fatigue and asthenia.
1 Musculoskeletal and connective tissue disorders Musculoskeletal pain Includes arthralgia, back pain, bone pain, musculoskeletal chest pain, myalgia, non-cardiac chest pain, osteoarthritis, pain in extremity, and spinal pain. 1 Gastrointestinal disorders Diarrhea Includes diarrhea, gastroenteritis, and immune-mediated enterocolitis.
1 Nausea 16 0 Constipation 15 0 Abdominal pain Includes abdominal pain, abdominal discomfort, and abdominal pain upper. 1 Infections and infestations Non-urinary tract infections Includes anal abscess, cellulitis, cholangitis, cholecystitis, cholecystitis acute, device related infection, herpes zoster, Lyme disease, pelvic infection, peritonitis, Pneumocystis jirovecii pneumonia, pneumonia, postoperative wound infection, pseudomonas infection, sepsis, skin infection, stoma site infection, and wound infection bacterial.
21 12 Urinary tract infection Includes urinary tract infection, cystitis, escherichia urinary tract infection, and pyelonephritis. 1 Reproductive system and breast disorders Perineal pain Includes anorectal discomfort, pelvic pain, proctalgia, and vulvovaginal discomfort.
19 7 Vascular disorders Hemorrhage Includes epistaxis, hematochezia, hematuria, proctitis hemorrhagic, rectal hemorrhage, stoma site hemorrhage, and vaginal hemorrhage. 2 Skin and subcutaneous tissue disorders Rash Includes rash, dermatitis, dermatitis acneiform, eczema, erythema, palmar-plantar erythrodysesthesia syndrome, rash erythematous, and rash maculo-papular.
1 Pruritus 12 0 Metabolism and nutrition disorders Decreased appetite Includes decreased appetite and hypophagia. 2 Cough Includes cough and productive cough. 0.
Table 6:
Laboratory Abnormalities that Worsened from Baseline to Grade 3 or 4 Occurring in ≥ 1% of Patients with Platinum-Refractory Locally Recurrent or Metastatic SCAC Receiving ZYNYZ in POD1UM-202 Laboratory abnormality ZYNYZ The denominator used to calculate the rate varied from 59 to 87 based on the number of patients with a baseline value and at least one post-treatment value.
0. 2)] . Patients received ZYNYZ 500 mg intravenously every 4 weeks until disease progression, unacceptable toxicity, or up to 24 months. 3 months (range: 1 day to 25 months). Serious adverse reactions occurred in 26% of patients receiving ZYNYZ.
The most frequent serious adverse reactions (≥ 2% of patients) were fatigue, arrhythmia, and pneumonitis. Permanent discontinuation of ZYNYZ due to an adverse reaction occurred in 21% of patients. These included asthenia, colitis, demyelinating polyneuropathy, diarrhea, drug hypersensitivity, eosinophilic fasciitis, hepatitis, hypophysitis, increased transaminases, infusion-related reaction, pancreatitis, polyarthritis, radiculopathy, toxic epidermal necrolysis, and tubulointerstitial nephritis (1 patient each).
Dosage interruptions due to an adverse reaction occurred in 39% of patients who received ZYNYZ. Adverse reactions or laboratory abnormalities that required dosage interruption in > 2% of patients who received ZYNYZ were increased transaminases, increased lipase, increased amylase, and pyrexia.
The most common (≥ 10%) adverse reactions that occurred in patients receiving ZYNYZ were musculoskeletal pain, fatigue, pruritus, diarrhea, rash, pyrexia, nausea, and constipation. Table 7 and Table 8 summarize adverse reactions and laboratory abnormalities, respectively, that occurred in POD1UM-201.
0. Adverse Reaction ZYNYZ (N = 107) All Grades (%) Grades 3-4 (%) Musculoskeletal and connective tissue disorders Musculoskeletal pain Includes arthralgia, back pain, bone pain, pain in extremity, neck pain, myalgia, and musculoskeletal chest pain.
37 3 General disorders and administration site conditions Fatigue Includes fatigue and asthenia. 33 1 Pyrexia 12 0 Skin and subcutaneous tissue disorders Pruritus 22 0 Rash Includes rash, dermatitis, dermatitis bullous, rash erythematous, rash maculo-papular, rash papular, rash pruritic, psoriasis, and toxic epidermal necrolysis.
0. ZYNYZ The denominator used to calculate the rate varied from 96 to 101 based on the number of patients with a baseline value and at least one post-treatment value. Laboratory Abnormality All Grades (%) Grades 3-4 (%) Hematology Decreased lymphocytes 31 11 Decreased neutrophils 14 3 Chemistry Increased lipase 39 5 Increased aspartate aminotransferase 28 3 Decreased sodium 27 3 Increased alanine aminotransferase 26 4 Increased alkaline phosphatase 22 2 Decreased potassium 15 2
Immune-mediated adverse reactions affecting more than one body system can occur simultaneously. Early identification and management of immune‐mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1–blocking antibodies.
Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.
In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. 2 )] .
In general, if ZYNYZ requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month.
Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids. , endocrinopathies and dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis ZYNYZ can cause immune-mediated pneumonitis.
In patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. 3%). 1% of patients. Systemic corticosteroids were required in 71% (10/14) of patients with pneumonitis.
Pneumonitis resolved in 11 of the 14 patients. Of the 5 patients in whom ZYNYZ was withheld for pneumonitis, 4 reinitiated ZYNYZ after symptom improvement; of these, 1 had recurrence of pneumonitis. Immune-Mediated Colitis ZYNYZ can cause immune-mediated colitis.
Cytomegalovirus infection/reactivation have occurred in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1–blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.
1%). 3% of patients. Systemic corticosteroids were required in 75% (9/12) of patients. Colitis resolved in 8 of the 12 patients. Of the 6 patients in whom ZYNYZ was withheld for colitis, 1 reinitiated ZYNYZ after symptom improvement; this patient did not have recurrence of colitis.
2%). Colitis led to permanent discontinuation of ZYNYZ in 2 patients and withholding of ZYNYZ in 2 patients. Systemic corticosteroids were required in 94% (15/16) of patients. Colitis resolved in 15 of the 16 patients. Of the 2 patients in whom ZYNYZ was withheld for colitis, both reinitiated ZYNYZ after symptom improvement; neither patient had a recurrence of colitis.
Immune-Mediated Hepatitis ZYNYZ can cause immune-mediated hepatitis. 9%). 1% of patients. Systemic corticosteroids were required in 81% (13/16) of patients. Hepatitis resolved in 9 of the 16 patients. Of the 5 patients in whom ZYNYZ was withheld for hepatitis, 3 reinitiated ZYNYZ after symptom improvement; of these, 1 had recurrence of hepatitis.
Immune-Mediated Endocrinopathies Adrenal Insufficiency ZYNYZ can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated.
2 )] . 4%). Adrenal insufficiency did not lead to permanent discontinuation of ZYNYZ. ZYNYZ was withheld for 1 patient with adrenal insufficiency. All patients required systemic corticosteroids. Adrenal insufficiency resolved in 1 of the 4 patients.
9% each). Adrenal insufficiency led to permanent discontinuation of ZYNYZ in 1 patient and withholding of ZYNYZ in 3 patients. All patients required systemic corticosteroids. Adrenal insufficiency resolved in 4 of the 9 patients. Hypophysitis ZYNYZ can cause immune-mediated hypophysitis.
Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. 2 )] . 4%). Hypophysitis led to permanent discontinuation of ZYNYZ in 1 patient and withholding of ZYNYZ in 1 patient.
All patients required systemic steroids. Hypophysitis resolved in 1 of the 3 patients. Thyroid Disorders ZYNYZ can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism.
Initiate hormone replacement or medical management of hyperthyroidism as clinically indicated. 2 )] . 7% (3/452, all Grade 1) of patients receiving ZYNYZ. No patients discontinued or withheld ZYNYZ due to thyroiditis. Thyroiditis resolved in 1 of the 3 patients.
9%). No patients discontinued ZYNYZ due to hypothyroidism. 4% of patients. Systemic corticosteroids were required for 1 patient and 78% (36/46) of patients received endocrine therapy. 7%). No patients discontinued ZYNYZ due to hyperthyroidism.
4% of patients. Systemic corticosteroids were required for 15% (4/26) of patients and 50% (13/26) of patients received endocrine therapy. Type 1 Diabetes Mellitus, Which Can Present with Diabetic Ketoacidosis Monitor patients for hyperglycemia or other signs and symptoms of diabetes.
Initiate treatment with insulin as clinically indicated. 2 )] . 2%). This event led to ZYNYZ being withheld and did not lead to permanent discontinuation of ZYNYZ. The patient received insulin. Immune-Mediated Nephritis with Renal Dysfunction ZYNYZ can cause immune-mediated nephritis.
4%). 7% of patients. Systemic corticosteroids were required in 67% (6/9) of patients. Nephritis resolved in 4 of the 9 patients. Of the 3 patients in whom ZYNYZ was withheld for immune-mediated nephritis, 1 reinitiated ZYNYZ after symptom improvement and did not have recurrence of immune-mediated nephritis.
Immune-Mediated Dermatologic Adverse Reactions ZYNYZ can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/PD-L1–blocking antibodies.
Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. 2 )] . 1%), and Grade 2 (8%). 7% of patients. Systemic corticosteroids were required in 33% (14/43) of patients. Immune-mediated dermatologic adverse reactions resolved in 72% (31/43) of patients.
Of the 12 patients in whom ZYNYZ was withheld for immune-mediated dermatologic adverse reactions, 8 reinitiated ZYNYZ after symptom improvement; of these, 2 had recurrence of immune-mediated dermatologic adverse reactions. 1 )] or were reported with the use of other PD-1/PD-L1–blocking antibodies, including severe or fatal cases.
Cardiac/vascular: myocarditis, pericarditis, vasculitis Gastrointestinal: pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis Musculoskeletal: myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis, polymyalgia rheumatica Neurological: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy Ocular: uveitis, iritis, and other ocular inflammatory toxicities.
Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt‑Koyanagi-Harada–like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
Endocrine: hypoparathyroidism Hematologic/Immune: 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.
Other:
Myocarditis-Myositis-Myasthenia Gravis (or Myasthenia-Like) Overlap Syndrome, reported as the co-occurrence of either two or all three adverse reactions. 1 )] . Monitor patients for signs and symptoms of infusion‑related reactions. 2 )] .
Consider premedication with an antipyretic and/or an antihistamine for patients who have had previous systemic reactions to infusions of therapeutic proteins. 3 Complications of Allogeneic HSCT Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1–blocking antibody.
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).
These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1–blocking antibody prior to or after an allogeneic HSCT.
4 Embryo-Fetal Toxicity Based on its mechanism of action, ZYNYZ can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus, resulting in fetal death.
Advise women of the potential risk to a fetus. 3 )] .