Mogamulizumab-kpkc is a CC chemokine receptor type 4 (CCR4)-directed monoclonal antibody indicated for the treatment of adult patients with relapsed or refractory mycosis fungoides or Sezary syndrome after at least 1 prior systemic therapy. Fatal and life-threatening skin reactions and infusion-related reactions have been reported with mogamulizumab therapy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Administer premedications (e.g., acetaminophen, diphenhydramine) prior to the mogamulizumab infusion as recommended; hold therapy for infusion-related reactions.
-If a dose is missed, administer mogamulizumab as soon as possible and resume the dosing schedule; the mogamulizumab dose should be given within 2 days of the scheduled dose.
Dilution:
-Withdraw the calculated dose from the mogamulizumab 4 mg/mL vial(s) and add to a polyvinyl chloride (PVC) or polyolefin (PO) infusion bag containing 0.9% sodium chloride injection for a final concentration between 0.1 to 3 mg/mL.
-Discard any unused portion of drug left in the vial.
-Gently invert the diluted solution to mix; do not shake.
-Storage following dilution: Use the diluted solution immediately or store under refrigeration (2 to 8 degrees C; 36 to 46 degrees F) for up to 24 hours from the time of preparation; do not freeze.
Intravenous (IV) Infusion:
-Infuse over at least 60 minute through an IV line containing a sterile, low protein binding, 0.22 micron (or equivalent) in-line filter.
-Do not mix with other drugs or coadminister through the same IV line.
Serious dermatologic adverse events including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with mogamulizumab therapy; some cases were fatal. Other skin rashes included lichenoid, spongiotic, or granulomatous dermatitis; psoriaform rash; morbilliform rash; and scaly plaques. Grade 3 dermatologic adverse events occurred in 3.6% of patients who received mogamulizumab in clinical trials (n = 528); grade 4 skin reactions and SJS both occurred in less than 1% of patients. Monitor patients for signs of rash during mogamulizumab therapy. A skin biopsy may be necessary to distinguish drug eruption from disease progression. Consider starting topical corticosteroids in patients who develop mild rash; give at least 2 weeks of topical corticosteroid therapy in patients who develop grade 2 or 3 rash. Mogamulizumab therapy may need to be held or discontinued in patients who develop a rash. If SJS or TEN is suspected, hold mogamulizumab therapy until SJS or TEN has been excluded and the cutaneous reaction has resolved to grade 1 or less. Permanently discontinue mogamulizumab in patients who develop SJS or TEN. Rash including drug eruption (35%; grade 3 or higher, 5%), drug eruption (24%; grade 3 or higher, 5%), xerosis (8%), and alopecia (7%) were reported in patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial. In a total of 319 patients who received mogamulizumab in this trial (including patients who crossed over from another treatment arm), drug eruption occurred in 25% of patients (grade 3, 17%). The median time to rash onset was 15 weeks. The term(s) rash/drug eruption included atopic dermatitis, contact dermatitis, exfoliative dermatitis, bullous rash, palmoplantar keratoderma, maculopapular rash, pruritic rash, pustular rash, and skin reaction.
Infection (e.g., sepsis and pneumonia) has been reported in patients who received mogamulizumab in clinical trials; some cases were fatal or life-threatening. Grade 3 or higher infection or an infection-related serious adverse reaction occurred in 18% of mogamulizumab-treated patients in a clinical trial. Monitor patients for signs or symptoms of infection; treat infections promptly. Upper respiratory tract infection (22%), skin infection (19%; grade 3 or higher, 3%), candidiasis (9%), urinary tract infection (9%), folliculitis (8%), pneumonia (6%), otitis (5%), herpes virus infection (5%), and cytomegalovirus infection (less than 1%) were reported in patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial. The term upper respiratory tract infection included viral laryngitis, nasopharyngitis, pharyngitis, rhinitis, and sinusitis. The term skin infection included cellulitis/periorbital cellulitis, infected dermatitis, erysipelas, impetigo, and infected skin ulcer.
Musculoskeletal pain (22%; grade 3 or higher, less than 1%) and muscle cramps/spasms (5%) were reported in patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial. The term musculoskeletal pain included back pain, bone pain, musculoskeletal chest pain, myalgia, neck pain, and extremity pain.
Grade 3 or higher immune-mediated reactions such as myositis, myocarditis, polymyositis, hepatitis, pneumonitis, glomerulonephritis, and a variant of Guillain-Barre syndrome have been reported with mogamulizumab therapy; some cases were fatal. Therapy interruption or discontinuation may be necessary in patients who are suspected of having or who develop immune-mediated adverse reactions. Systemic immunosuppressants were administered in 1.9% of patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 319) in a randomized clinical trial; one case was for the treatment of polymyalgia rheumatica. Additionally, new-onset hypothyroidism was reported in 1.3% of patients in this trial; patients were managed with observation or levothyroxine therapy.
Hepatitis B exacerbation was reported in postmarketing surveillance of mogamulizumab.
Serious adverse events including grade 3 or 4 graft-versus-host disease (GVHD) and transplant-related death have occurred in patients who received an allogeneic hematopoietic stem-cell transplant within approximately 50 days prior to or after treatment with mogamulizumab. Monitor patients closely for early evidence of transplant-related complications.
Fever (17%; grade 3 or higher, less than 1%) and chills (7%) were reported in patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial.
Gastrointestinal adverse events including diarrhea (28%), nausea (16%), constipation (13%), mucositis (12%; grade 3 or higher, 1%), anorexia/decreased appetite (8%), vomiting (7%), and abdominal pain (5%) were reported in patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial. The term mucositis included aphthous stomatitis, mouth/oral ulceration, mucosal inflammation, oral discomfort, oral pain, oropharyngeal pain, and stomatitis.
Edema was reported in 16% of patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial.
Fatigue was reported in 31% of patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial.
Thrombocytopenia (14%) and anemia (12%) occurred in patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial. Treatment-emergent anemia (35%; grade 3 or 4, 2%), thrombocytopenia (29%), neutropenia (10%; grade 3 or 4, 2%), decreased CD4 lymphocyte level (63%; grade 3 or higher, 43%), decreased lymphocyte level (31%; grade 3 or higher, 16%), decreased white blood cell level (33%; grade 3 or higher, 2%), grade 4 lymphopenia (5%), and grade 4 leukopenia (1%) were also reported.
Headache (14%), dizziness (8%), peripheral neuropathy (7%), and fall (6%) were reported in patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial.
Cardiovascular adverse events including hypertension (10%), arrhythmia (5%), heart failure (less than 1%), and myocardial infarction/ischemia (less than 1%) were reported in patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial. Stress cardiomyopathy was reported in postmarketing surveillance of mogamulizumab.
Cough (11%) and dyspnea (7%) were reported in patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial.
Insomnia (9%) and depression (7%) were reported in patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial.
Nephrotoxicity, specifically renal insufficiency, was reported in 9% of patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial.
Hyperglycemia was reported in 9% of patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial. Treatment-emergent hyperglycemia (52%; grade 3 or 4, 4%) and decreased glucose level/hypoglycemia (14%) occurred in patients who received mogamulizumab in this trial.
Hyperuricemia (8%) and tumor lysis syndrome (TLS) (less than 1%) were reported in patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial. Grade 3 or higher treatment-emergent increased uric acid level occurred in 29% of patients who received mogamulizumab in this trial.
Weight gain was reported in 8% of patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial.
Weight loss was reported in 6% of patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial.
Hypomagnesemia was reported in 6% of patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial. Treatment-emergent decreased albumin level/hypoalbuminemia (34%; grade 3 or higher, 2%), decreased phosphate level (27%; grade 3 or higher, 5%), decreased magnesium level (17%; grade 3 or higher, less than 1%), decreased calcium level/hypocalcemia (30%; grade 3 or higher, 3%), increased calcium level/hypercalcemia (12%; grade 3 or higher, less than 1%), and grade 4 hypophosphatemia (1%) occurred in patients who received mogamulizumab in this trial.
Conjunctivitis was reported in 5% of patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial.
Antibody formation (detection of anti-mogamulizumab-kpkc antibodies) was reported in 14.1% of patients who received mogamulizumab (n = 313) in a clinical trial. Anti-drug antibodies had no clinically significant impact on the pharmacokinetics, safety, or effectiveness of mogamulizumab. No positive neutralizing antibody responses were detected.
Treatment-emergent elevated hepatic enzymes including increased AST level (25%; grade 3 or 4, 2%), increased ALT level (18%; grade 3 or 4, 1%), and increased alkaline phosphatase level (17%) were reported in patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial.
Infusion-related reactions have been reported in 35% of patients who received mogamulizumab in a clinical trial; some cases were fatal or life-threatening. Most reactions occurred during or shortly after the first infusion. Reactions may include chills, nausea, fever, sinus tachycardia, rigors, headache, and vomiting. Premedicate patients with acetaminophen and diphenhydramine prior the mogamulizumab infusion if a reaction occurs. Monitor patients for signs and symptoms of infusion reactions; treat symptoms promptly. The mogamulizumab infusion may need to be held or discontinued in patients who develop an infusion reaction. Infusion-related reactions were reported in 33% of patients with relapsed or refractory mycosis fungoides or Sezary syndrome who received mogamulizumab (n = 184) in a randomized clinical trial; grade 3 or higher infusion-related reactions occurred in 2% of patients. In a total of 319 patients who received mogamulizumab in this trial (including patients who crossed over from another treatment arm), infusion-related reactions occurred in 35% of patients (grade 3, 8%). Additionally, infusion reactions occurred in 42% of patients who did not receive premedication and 32% of patients who did receive premedication.
Serious rash including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) has been reported with mogamulizumab use; some cases were fatal. Monitor patients for signs of rash during mogamulizumab therapy. A skin biopsy may be necessary to distinguish drug eruption from disease progression. Consider starting topical corticosteroids in patients who develop mild rash; give at least 2 weeks of topical corticosteroid therapy in patients who develop grade 2 or 3 rash. Mogamulizumab therapy may need to be held or discontinued in patients who develop a rash. If SJS or TEN is suspected, hold mogamulizumab therapy until SJS or TEN has been excluded and the cutaneous reaction has resolved to grade 1 or less. Permanently discontinue mogamulizumab in patients who develop SJS or TEN.
Fatal and life-threatening infusion-related reactions have been reported with mogamulizumab therapy; most reactions occurred during or shortly after the first infusion. Premedicate patients with acetaminophen and diphenhydramine prior to the first mogamulizumab infusion and prior to subsequent infusions if a reaction occurs. Monitor patients for signs and symptoms of infusion reactions (e.g., chills, nausea, fever, tachycardia, rigors, headache, and/or vomiting); treat symptoms promptly. The mogamulizumab infusion may need to be held or discontinued in patients who develop an infusion reaction.
Infection (e.g., sepsis, pneumonia, skin infection) has been reported with mogamulizumab therapy; some cases were fatal. Monitor patients for signs or symptoms of infection; treat infections promptly.
Fatal and life-threatening immune-mediated reactions (e.g., myositis, myocarditis, polymyositis, hepatitis, pneumonitis, glomerulonephritis, and a variant of Guillain-Barre syndrome) have been reported with mogamulizumab therapy. Therapy interruption or discontinuation may be necessary in patients who are suspected of having or who develop immune-mediated adverse reactions. Weigh the risks versus benefits of starting mogamulizumab in patients with a history of autoimmune disease.
Patients who receive an allogeneic stem cell transplant within approximately 50 days of receiving mogamulizumab or after mogamulizumab therapy have an increased risk of serious transplant-related complications including grade 3 or 4 graft versus host disease and transplant-related death. Monitor these patients closely for early evidence of transplant-related complications.
It is not known if mogamulizumab causes fetal harm when administered to pregnant women; therefore, mogamulizumab is not recommended during pregnancy or in women of reproductive potential who are not using contraception. Immunoglobulin G1 (IgG1) monoclonal antibodies are transferred across the placenta. However, no adverse developmental outcomes occurred in the offspring of pregnant cynomolgus monkeys following mogamulizumab doses that resulted in 27-times the exposure observed at the recommended human dose.
Counsel patients about the reproductive risk and contraception requirements during mogamulizumab treatment. Pregnancy testing should be performed prior to starting mogamulizumab in female patients of reproductive potential. These patients avoid pregnancy and use effective contraception during and for 3 months after the last mogamulizumab dose.
It is not known if mogamulizumab is secreted in human milk or if it has effects on the breast-fed infant or on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.
For the treatment of cutaneous T-cell lymphoma (CTCL), specifically mycosis fungoides or sezary syndrome, in patients who have received at least 1 prior systemic therapy:
NOTE: Mogamulizumab has been designated by the FDA as an orphan drug for the treatment of patients with CTCL.
Intravenous dosage:
Adults: 1 mg/kg IV on days 1, 8, 15, and 22 in cycle 1 then mogamulizumab 1 mg/kg IV on days 1 and 15 in subsequent cycles until disease progression; therapy cycles are repeated every 28 days. Patients should receive premedication with acetaminophen and diphenhydramine prior to the first infusion and prior to subsequent infusions if a reaction occurs. Therapy interruption or discontinuation may be necessary in patients who develop severe toxicity. The investigator-assessed median progression-free survival (PFS) time (primary endpoint) was significantly prolonged in patients with relapsed or refractory, stage IB to IVB mycosis fungoides or Sezary syndrome who received mogamulizumab compared with vorinostat (7.7 months vs. 3.1 months; hazard ratio (HR) = 0.53; 95% CI, 0.41 to 0.69) in a multinational, randomized, phase 3 trial (n = 372; MAVORIC trial) at a median follow-up of 17 months. Significantly improved PFS time with mogamulizumab therapy was confirmed in an independent review (6.7 months vs. 3.8 months; HR = 0.64; 95% CI, 0.49 to 0.84). Patients (median age, 64 years; range, 25 to 101 years) in this trial had received a median of 3 prior systemic therapies.
Therapeutic Drug Monitoring:
Management of Treatment-Related Toxicity
Dermatologic Toxicity
Grade 1 (mild) rash: consider initiating topical corticosteroids.
Grade 2 or 3 rash: hold mogamulizumab therapy and administer at least 2 weeks of topical corticosteroids; if the rash improves to grade 1 or less, resume mogamulizumab therapy.
Grade 4 (life-threatening) rash or Stevens-Johnson syndrome or toxic epidermal necrolysis: permanently discontinue mogamulizumab.
Infusion-Related Reactions
Grade 1 to 3 toxicity: stop the infusion and treat symptoms; resume the infusion at no more than 50% of the previous rate after the symptoms resolve and continue premedication (e.g., acetaminophen, diphenhydramine) prior to each subsequent dose. Discontinue mogamulizumab therapy if the reaction recurs and is unmanageable.
Grade 4 (life-threatening) toxicity: permanently discontinue mogamulizumab.
Maximum Dosage Limits:
-Adults
1 mg/kg/dose IV.
-Geriatric
1 mg/kg/dose IV.
-Adolescents
Safety and efficacy not established.
-Children
Safety and efficacy not established.
-Infants
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Mogamulizumab-kpkc is a defucosylated, humanized IgG1 kappa monoclonal antibody that binds to CC chemokine receptor type 4 (CCR4), a G protein-coupled receptor for CC chemokines that is involved in the trafficking of lymphocytes to various organs. CCR4 is expressed on the surface of T-cell malignancies, including some types of cutaneous T-cell lymphoma (CTCL). CCR4 and its chemokine ligands are overexpressed in CTCL skin lesions at all stages of disease.
Nonclinical data demonstrate that mogamulizumab binding targets a cell for antibody-dependent cellular cytotoxicity (ADCC) resulting in depletion of the target cells. Although there have been no reports of resistance with mogamulizumab therapy, resistance could occur via loss of CCR4 expression, a mutation or deletion within the epitope coding region of mogamulizumab, an increase in soluble CCR4, and reduced ADCC.
Mogamulizumab is administered as an intravenous infusion. It has a central volume of distribution of 3.6 L (coefficient of variation (CV), 20%), a terminal half-life of 17 days (CV, 66%), and a clearance of 12 mL/hour (CV, 84%). Mogamulizumab concentrations increase proportionally over a dose range of 0.01 to 1 mg/kg in patients with T-cell malignancies.
-Route-Specific Pharmacokinetics
Intravenous Route
Steady state concentrations were reached following 12 weeks of mogamulizumab therapy (8 doses); the systemic accumulation was 1.6-fold. The mogamulizumab Cmax, Cmin, and AUC values were 32 mcg/mL(CV, 68%), 11 mcg/mL (239%), and 5,577 mcg x hour/mL(CV, 125%), respectively, at steady state.
-Special Populations
Hepatic Impairment
Mild (total bilirubin level up to 1.5-times the upper limit of normal (ULN) and any AST level) or moderate (total bilirubin level greater than 1.5-times to 3-times the ULN and any AST level) hepatic impairment does not significantly impact the pharmacokinetic (PK) parameters of mogamulizumab. The effect of severe hepatic impairment on the PK parameters of mogamulizumab has not been evaluated.
Renal Impairment
Renal impairment (creatinine clearance less than 90 mL/min) does not significantly impact the pharmacokinetic parameters of mogamulizumab.
Geriatric
Age (range, 22 to 101 years) does not significantly impact the pharmacokinetic parameters of mogamulizumab.
Gender Differences
Gender does not significantly impact the pharmacokinetic parameters of mogamulizumab.
Ethnic Differences
Ethnicity does not significantly impact the pharmacokinetic parameters of mogamulizumab.
Other
Disease subtype (mycosis fungoides or Sezary syndrome), degree of CCR4 expression, or ECOG status does not significantly impact the pharmacokinetic parameters of mogamulizumab.