Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Poteligeo: mogamulizumab-kpkc 20 mg/5 mL (5 mL) [contains polysorbate 80]
Pharmacology
Mechanism of Action
Mogamulizumab is a first-in-class defucosylated, humanized IgG1 kappa monoclonal antibody which selectively binds to C-C chemokine receptor 4 (CCR4). CCR4 mediates cell trafficking of lymphocytes to skin and various organs and is consistently expressed on the surface of T-cell malignancies (eg, mycosis fungoides, Sézary syndrome, adult T-cell leukemia/lymphoma, peripheral T-cell lymphoma) (Kim 2018). Mogamulizumab binding to CCR4 targets a cell for antibody-dependent cellular cytotoxicity (ADCC), resulting in target cell depletion.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: 3.6 L
Half-Life Elimination
17 days
Use: Labeled Indications
Mycosis fungoides, relapsed or refractory: Treatment of adult patients with relapsed or refractory mycosis fungoides (MF) after at least one prior systemic therapy.
Sézary syndrome, relapsed or refractory: Treatment of adult patients with relapsed or refractory Sézary syndrome (SS) after at least one prior systemic therapy.
Contraindications
There are no contraindications listed in the manufacturer's labeling.
Dosage and Administration
Dosing: Adult
Note: Administer premedication (diphenhydramine and acetaminophen) prior to the first mogamulizumab infusion, as well as subsequent doses if an infusion reaction occurs during the first dose. Treatment cycles are 28 days in length.
Mycosis fungoides, relapsed or refractory: IV: 1 mg/kg on days 1, 8, 15, and 22 of cycle 1, followed by 1 mg/kg on days 1 and 15 of each subsequent cycle; continue until disease progression or unacceptable toxicity (Kim 2018).
Sézary syndrome, relapsed or refractory: IV: 1 mg/kg on days 1, 8, 15, and 22 of cycle 1, followed by 1 mg/kg on days 1 and 15 of each subsequent cycle; continue until disease progression or unacceptable toxicity (Kim 2018).
Missed doses: Administer mogamulizumab within 2 days of the scheduled dose; if a dose is missed, administer the next dose as soon as possible and resume dosing schedule.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Adjustment for Toxicity
Autoimmune toxicity: Consider therapy interruption or permanent discontinuation; evaluate the risk/benefit of mogamulizumab therapy in patients with a history of autoimmune disease.
Dermatologic toxicity:
Grade 1 rash (mild): Consider topical corticosteroids.
Grade 2 or 3 rash (moderate or severe): Interrupt mogamulizumab therapy and administer at least 2 weeks of topical corticosteroids. If rash improves to ≤ grade 1, may resume therapy.
Grade 4 rash (life-threatening), Stevens-Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN): Permanently discontinue mogamulizumab for grade 4 rash, confirmed SJS, or TEN. If SJS/TEN is suspected, interrupt mogamulizumab therapy and do not resume unless SJS/TEN has been ruled out and the cutaneous reaction has improved to ≤ grade 1.
Infusion reactions:
Grade 1, 2, or 3 (mild, moderate, or severe): Temporarily interrupt infusion and manage symptoms as clinically necessary. After symptoms resolve, resume the infusion with the rate reduced by at least 50% (administer premedication with diphenhydramine and acetaminophen prior to subsequent infusions). If the reaction recurs and is unmanageable, discontinue mogamulizumab.
Grade 4 (life-threatening): Permanently discontinue mogamulizumab.
Reconstitution
Withdraw the required volume of mogamulizumab into a syringe and transfer to an IV bag containing NS. The final concentration of the diluted solution should be between 0.1 to 3 mg/mL. Gently invert to mix; do not shake. Discard any unused medication left in the vial. Solution diluted for infusion is compatible with polyvinyl chloride (PVC) or polyolefin (PO) infusion bags.
Administration
IV: Administer IV over at least 60 minutes through an IV line containing a sterile, low protein binding, 0.22 micron (or equivalent) in-line filter. Do not administer subcutaneously or by rapid IV administration. Do not mix mogamulizumab with any other medications or infuse other medications through the same line.
Premedicate prior to the first infusion with diphenhydramine and acetaminophen. If a mild or moderate infusion reaction occurs (grade 1 to 3), temporarily interrupt infusion until symptoms resolve and resume infusion with the rate reduced by at least 50% (premedicate prior to subsequent infusions). Permanently discontinue for life-threatening (grade 4) infusion reactions.
Storage
Store intact vials at 2°C to 8°C (36°F to 46°F). Store in original package to protect from light until time of use. Do not freeze. Do not shake. If not used immediately, solution diluted for infusion may be stored at 2°C to 8°C (36°F to 46°F) for no more than 4 hours from the time of preparation; do not freeze or shake diluted solution.
Drug Interactions
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy
Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification
Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination
Adverse Reactions
>10%:
Cardiovascular: Edema (16%)
Central nervous system: Fatigue (31%), headache (14%)
Dermatologic: Skin rash (25% to 35%; including granulomatous and psoriasiform dermatitis, folliculitis, lichenoid, maculopapular, morbilliform, papular, and spongiotic rash, pustular eruption, and scaly plaques), skin infection (19%)
Endocrine & metabolic: Hyperglycemia (9% to 52%), decreased serum albumin (34%), decreased serum calcium (30%), increased uric acid (29%), decreased serum magnesium (17%), decreased serum glucose (14%), increased serum calcium (12%)
Gastrointestinal: Diarrhea (28%), nausea (16%), constipation (13%), mucositis (12%)
Hematologic & oncologic: Decreased T cell lymphocytes (CD4: 63%; ≥ grade 3: 43%), anemia (12% to 35%; grades 3/4: 2%), decreased white blood cell count (33%; ≥ grade 3: 2%), lymphocytopenia (5% to 31%; ≥ grade 3: 16%), thrombocytopenia (14% to 29%)
Hepatic: Increased serum aspartate aminotransferase (25%), increased serum alanine aminotransferase (18%), increased serum alkaline phosphatase (17%)
Hypersensitivity: Fixed drug eruption (24%)
Neuromuscular & skeletal: Musculoskeletal pain (22%)
Respiratory: Upper respiratory tract infection (22%), cough (11%)
Miscellaneous: Infusion-related reaction (33% to 35%; including chills, fever, headache, nausea, rigors, tachycardia, and vomiting), fever (17%)
1% to 10%:
Cardiovascular: Hypertension (10%), cardiac arrhythmia (5%)
Central nervous system: Insomnia (9%), dizziness (8%), chills (7%), depression (7%), peripheral neuropathy (7%), falling (6%)
Dermatologic: Folliculitis (8%), xerosis (8%), alopecia (7%)
Endocrine & metabolic: Hyperuricemia (8%), weight gain (8%), hypomagnesemia (6%), weight loss (6%), hypophosphatemia (1%), hypothyroidism (1%; new-onset)
Gastrointestinal: Decreased appetite (8%), vomiting (7%), abdominal pain (5%)
Genitourinary: Urinary tract infection (9%)
Hematologic & oncologic: Neutropenia (10%; grades 3/4: 2%), leukopenia (1%)
Immunologic: Antibody development (4%)
Infection: Candidiasis (9%), herpes virus infection (5%)
Neuromuscular & skeletal: Muscle spasm (5%)
Ophthalmic: Conjunctivitis (5%)
Otic: Otitis (5%)
Renal: Renal insufficiency (9%)
Respiratory: Dyspnea (7%), pneumonia (6%)
Frequency not defined:
Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis
Hepatic: Hepatitis
Hypersensitivity: Type III hypersensitivity reaction (including hepatitis, myocarditis, myositis, pneumonitis, polymyositis, and a variant of Guillain-Barre syndrome)
Infection: Sepsis
Respiratory: Lower respiratory tract infection, pneumonitis
<1%, postmarketing, and/or case reports: Cardiac failure, cardiomyopathy (stress), ischemic heart disease, myocardial infarction, reactivation of HBV, tumor lysis syndrome
Warnings/Precautions
Concerns related to adverse effects:
- Autoimmune toxicity: Life-threatening and fatal immune-mediated complications have occurred in patients receiving mogamulizumab. Grade 3 or higher immune-mediated (or possibly immune-mediated) reactions included myositis, myocarditis, polymyositis, hepatitis, pneumonitis, and a variant of Guillain-Barré syndrome; some patients received systemic immunosuppressants for the management of immune-mediated reactions. New-onset grade 1 or 2 hypothyroidism also occurred in a small number of patients, and was managed with observation or thyroid medication. Autoimmune-mediated toxicity may require therapy interruption and/or permanent discontinuation; consider the risk/benefit of mogamulizumab therapy in patients with a history of autoimmune disease.
- Bone marrow suppression: Lymphocytopenia (including CD4 lymphocytes) may commonly occur; including ≥ grade 3 events. Leukopenia, anemia, thrombocytopenia, and neutropenia may also occur.
- Dermatologic toxicity: Dermatologic toxicity, including fatal and life-threatening reactions (eg, Stevens-Johnson syndrome [SJS], toxic epidermal necrolysis [TEN]), has occurred. Rash (drug eruption) is one of the most frequently reported toxicities of mogamulizumab therapy; in a clinical trial, the majority of rashes were grade 1 or 2, although grade 3 or 4 toxicity has also been reported. The median time to onset of drug eruption was 15 weeks (with one-quarter of cases occurring after 31 weeks). Papular or maculopapular rash, lichenoid, spongiotic or granulomatous dermatitis, and morbilliform rash were the most common presentations of drug eruption; other clinical presentations included scaly plaques, pustular eruption, folliculitis, non-specific dermatitis, and psoriasiform dermatitis. Monitor for rash throughout mogamulizumab therapy; management may include topical corticosteroids, therapy interruption, and/or permanent discontinuation. Skin biopsy may be considered to distinguish dermatologic toxicity/drug eruption from disease progression. Interrupt therapy for suspected SJS or TEN, and do not reinitiate unless SJS/TEN is ruled out and cutaneous reaction has improved to ≤ grade 1. Discontinue mogamulizumab for confirmed SJS or TEN, or for life-threatening grade 4 reaction.
- Infections: Life-threatening and fatal infections have been reported, including sepsis, pneumonia, and skin infection. Close to 20% of patients experienced grade 3 or higher infection or an infection-related serious adverse reaction. Monitor for signs/symptoms of infection and manage promptly. Postmarketing identification of hepatitis B reactivation has been observed.
- Infusion reactions: Infusion reactions have been reported with mogamulizumab, including life-threatening and fatal events. The majority of reactions occur during or shortly after the first infusion, but may also occur with subsequent infusions. Commonly reported signs/symptoms include chills, nausea, fever, tachycardia, rigors, headache, and vomiting. Consider premedication (diphenhydramine and acetaminophen) prior to the first infusion in all patients, as well as in patients who experience an infusion reaction in previous cycles. Monitor closely for signs/symptoms of infusion reactions and interrupt the infusion for any grade reaction; manage promptly if infusion reactions develop; discontinue permanently for life-threatening (grade 4) infusion reaction.
Disease-related concerns:
- Hematopoietic stem cell transplant: Increased transplant complications have been reported in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) after mogamulizumab therapy, including grade 3 or 4 acute graft-versus-host disease (GVHD), steroid-refractory GVHD, and transplant-related death. A higher risk of transplant complications has been reported when mogamulizumab is administered within a shorter time frame (~50 days) before HSCT. Monitor closely for early evidence of transplant-related complications.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
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 renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Monitoring Parameters
Verify pregnancy status in females of reproductive potential prior to therapy initiation; monitor for dermatologic toxicity, signs/symptoms of infusion reactions, infections, and autoimmune-mediated reactions. Monitor closely for early evidence of transplant-related complications (in patients who receive hematopoietic transplant).
Pregnancy
Pregnancy Considerations
Adverse events were not observed in animal reproduction studies.
IgG molecules are known to cross the placenta. Evaluate pregnancy status prior to use. Effective contraception should be used in females of reproductive potential during treatment and for at least 3 months after mogamulizumab therapy is complete.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience diarrhea, constipation, nausea, vomiting, common cold symptoms, muscle pain, bone pain, mouth irritation, mouth sores, lack of appetite, weight gain, weight loss, trouble sleeping, dry skin, hair loss, abdominal pain, or eye redness. Have patient report immediately to prescriber signs of infusion reaction, signs of infection, signs of skin infection, signs of kidney problems (unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain), signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating), signs of electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting), severe headache, dizziness, passing out, vision changes, edema, bruising, bleeding, severe loss of strength and energy, depression, burning or numbness feeling, shortness of breath, abnormal heartbeat, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
