Mogamulizumab, a recombinant humanized anti-CC chemokine receptor 4 (anti-CCR4) monoclonal antibody, is an antineoplastic agent.1, 3, 10
Mycosis Fungoides or Sézary Syndrome
Mogamulizumab-kpkc is used for the treatment of relapsed or refractory mycosis fungoides or Sézary syndrome that has progressed following at least one prior systemic therapy.1, 3 Mogamulizumab has been designated an orphan drug by FDA for the treatment of cutaneous T-cell lymphoma.2 Currently available evidence indicates that mogamulizumab therapy is associated with substantially prolonged progression-free survival and improved overall response rates compared with vorinostat.1, 3
The current indication for mogamulizumab-kpkc is based principally on results of a randomized, open-label, multicenter phase 3 study (MAVORIC) in 372 adults with relapsed or refractory mycosis fungoides or Sézary syndrome that progressed following at least one systemic therapy.1, 3 Patients were randomized in a 1:1 ratio to receive either mogamulizumab-kpkc at the recommended dosage (1 mg/kg IV on days 1, 8, 15, and 22 of first 28-day cycle, then 1 mg/kg IV on days 1 and 15 of subsequent 28-day cycles) or vorinostat (400 mg orally once daily in 28-day cycles).1, 3 Treatment was continued until unacceptable toxicity or disease progression occurred.1, 3 Patients randomized to receive vorinostat were permitted to cross over to mogamulizumab-kpkc therapy following disease progression or unacceptable toxicity.1, 3 The primary measure of efficacy was investigator-assessed progression-free survival (as assessed by combined measures from each disease compartment using global composite response criteria).1, 3 Secondary measures of efficacy included overall response rate (as assessed by global composite response criteria) and duration of response; response was confirmed following 2 consecutive disease assessments (at least 8 weeks apart) using a modified Severity Weighted Assessment Tool [mSWAT], skin photography, central flow cytometry, and CT scan.1, 3
The median age of patients was 64 years; 70% were white, 38% had stage IB-II disease, 10% had stage III disease, and 52% had stage IV disease.1 Patients enrolled in the study had received a median of 3 prior systemic therapies.1 Among 140 mogamulizumab-treated patients with baseline CC chemokine receptor 4 (CCR4) expression status (as determined by immunohistochemistry), 100 or 96% of these patients had CCR4 expression on at least 1 or at least 10%, respectively, of lymphocytes on skin biopsy.1 Expression of CCR4 was similar in vorinostat-treated patients.1
At an estimated median follow-up of 13 or 10.4 months in patients receiving mogamulizumab-kpkc or vorinostat, respectively, median investigator-assessed progression-free survival was 7.6 months in patients receiving mogamulizumab-kpkc compared with 3.1 months in those receiving vorinostat.1 The results of the progression-free survival analysis based on investigator assessment were consistent with the assessment by an independent review committee.1, 3 In addition, patients receiving mogamulizumab-kpkc had higher overall response rates compared with those receiving vorinostat (28 versus 5%); complete responses were achieved in 2% of patients receiving mogamulizumab-kpkc and none of those receiving vorinostat.1 The median duration of response in patients receiving mogamulizumab-kpkc or vorinostat was 13.9 or 9 months, respectively.1 The median duration of exposure to mogamulizumab-kpkc or vorinostat was 5.6 or 2.8 months, respectively; approximately one-half (48%) or 23% of mogamulizumab-treated patients received the drug for at least 6 or 12 months, respectively, and 22% of vorinostat-treated patients received the drug for at least 6 months.1
Because of the risk of infusion-related reactions, the manufacturer recommends a premedication regimen (e.g., acetaminophen and diphenhydramine) prior to the initial mogamulizumab infusion.1 If an infusion-related reaction occurs, a premedication regimen also should be given prior to subsequent infusions of the drug.1
Mogamulizumab-kpkc is administered by IV infusion over at least 60 minutes.1 The drug should not be administered subcutaneously or by rapid IV administration.1
Unopened vials of mogamulizumab-kpkc injection should be stored at 2-8°C and retained in the original carton for protection from light; the vials should not be frozen.1
Mogamulizumab-kpkc injection and diluted solutions of the drug should be inspected visually for particulate matter and discoloration prior to administration.1 Solutions of the drug should be clear to slightly opalescent and colorless; the drug should be discarded if the solution is cloudy, discolored, or contains particulates.1 The vials should not be shaken.1
For preparation of the diluted mogamulizumab-kpkc solution for IV infusion, the appropriate dose of commercially available mogamulizumab-kpkc injection containing 4 mg/mL should be withdrawn from the appropriate number of vials and injected into a PVC or polyolefin infusion bag containing an appropriate volume of 0.9% sodium chloride injection to achieve a final concentration of 0.1-3 mg/mL.1 The diluted solution for infusion should be mixed by gentle inversion and should not be shaken.1
The diluted mogamulizumab-kpkc solution should be administered through a sterile, low-protein-binding 0.22-µm (or equivalent) inline filter.1
If immediate administration of diluted mogamulizumab-kpkc solution for infusion is not possible, the diluted solution of the drug may be stored for up to 4 hours after dilution under refrigeration (2-8°C); the diluted solution should not be frozen.1
Any unused portions in the vials or infusion bags should be discarded since mogamulizumab-kpkc injection contains no preservative.1
Mogamulizumab-kpkc should not be mixed with or administered simultaneously through the same IV line with other drugs.1
Mycosis Fungoides or Sézary Syndrome
For the treatment of relapsed or refractory mycosis fungoides or Sézary syndrome in adults, mogamulizumab-kpkc is administered in 28-day cycles until disease progression or unacceptable toxicity occurs.1 During cycle 1, the recommended dosage of mogamulizumab-kpkc is 1 mg/kg on days 1, 8, 15, and 22.1 During subsequent cycles, the same dosage of mogamulizumab-kpkc is administered on days 1 and 15 of each cycle.1
Mogamulizumab-kpkc may be administered within 2 days of a scheduled dose.1, 11 If a dose is missed, the dose of mogamulizumab-kpkc should be administered as soon as possible and the dosing schedule should be resumed.1
Therapy Interruption for Toxicity
If grade 2 or 3 rash occurs, mogamulizumab therapy should be interrupted.1 Once the toxicity has improved to grade 1 or less and topical corticosteroid therapy has been completed, mogamulizumab therapy may be resumed.1 (See Dermatologic Effects under Cautions: Warnings/Precautions.)
If Stevens-Johnson syndrome or toxic epidermal necrolysis is suspected, mogamulizumab therapy should be interrupted until such a diagnosis is excluded and the toxicity improves to grade 1 or less.1
If grade 4 rash occurs or Stevens-Johnson syndrome or toxic epidermal necrolysis is confirmed, mogamulizumab therapy should be permanently discontinued.1
If grade 1-3 infusion-related reactions occur, the infusion should be interrupted and appropriate treatment should be provided; once the reaction has resolved, the infusion may be resumed but the rate of infusion should be reduced by at least 50%.1 If the infusion-related reaction recurs and is unmanageable, mogamulizumab therapy should be discontinued.1 (See Infusion-related Effects under Cautions: Warnings/Precautions.)
If grade 4 infusion-related reactions occur, mogamulizumab therapy should be permanently discontinued.1
Immune-mediated Adverse Events
If an immune-mediated adverse effect is suspected, mogamulizumab therapy should be interrupted or permanently discontinued as appropriate.1 (See Immune-mediated Events under Cautions: Warnings/Precautions.)
No dosage adjustment is necessary in patients with mild or moderate hepatic impairment.11, 13 (See Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)
No dosage adjustment is necessary in patients with renal impairment.11, 13 (See Renal Impairment under Warnings/Precautions: Specific Populations, in Cautions.)
Dosage adjustment based solely on age is not required.11 (See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)
The manufacturer states there are no known contraindications to the use of mogamulizumab.1
Rash (including drug eruption), sometimes fatal or life-threatening (i.e., Stevens-Johnson syndrome, toxic epidermal necrolysis), has been reported in patients receiving mogamulizumab therapy.1, 3, 4, 5, 9, 10 Although the mechanism by which these adverse skin reactions occur has not been fully elucidated, it has been suggested that mogamulizumab-induced depletion of regulatory T-cells and subsequent abrogation of the peripheral immune checkpoint responsible for regulating autoantibody production may result in the elicitation of keratinocyte- and melanocyte-bound autoantibodies.5, 9
In the principal efficacy study, drug eruption occurred in 25% of patients receiving mogamulizumab-kpkc; grade 1-2 or 3 drug eruption was reported in 82 or 18%, respectively, of these patients.1 The most common presentation of drug eruption was papular or maculopapular rash, lichenoid, spongiotic dermatitis, granulomatous dermatitis, and morbilliform rash.1, 4 Drug eruption also presented as scaly plaques, pustular eruption, folliculitis, nonspecific dermatitis, or psoriasiform dermatitis.1, 4 The onset, affected area, and appearance of drug eruption associated with mogamulizumab therapy may vary.1 In the principal efficacy study, the median time to onset of drug eruption was 15 weeks; however, drug eruption occurred after 31 weeks in 25% of patients.1
In clinical trials, grade 3-4 skin reactions or Stevens-Johnson syndrome were reported in approximately 4.6 or less than 1%, respectively, of patients receiving mogamulizumab-kpkc.1
Patients should be monitored for skin reactions during mogamulizumab therapy.1 In patients who develop grade 1 rash, topical corticosteroid therapy should be considered.1 In patients who develop grade 2 or 3 rash, topical corticosteroid therapy should be initiated for a duration of at least 2 weeks.1 If Stevens-Johnson syndrome or toxic epidermal necrolysis is suspected, mogamulizumab therapy should be temporarily interrupted until such diagnosis has been excluded.1 If Stevens-Johnson syndrome or toxic epidermal necrolysis is confirmed, mogamulizumab therapy should be permanently discontinued.1 Temporary interruption or discontinuance of mogamulizumab therapy may be necessary if dermatologic reactions occur during therapy with the drug.1 (See Dermatologic Toxicity under Dosage: Therapy Interruption for Toxicity, in Dosage and Administration.) Because drug eruption may be visually indistinguishable from disease progression, clinicians should consider biopsy of the affected area.1, 9, 13
Infusion-related reactions, sometimes fatal or life-threatening, have been reported in patients receiving mogamulizumab therapy.1
In the principal efficacy study, infusion-related reactions occurred in 35% of patients receiving mogamulizumab-kpkc;1 8% of these infusion-related reactions were grade 3 in severity.1 Infusion-related reactions occurred more frequently during or shortly after the first infusion than during subsequent infusions of the drug.1 The most common infusion-related effects were chills, nausea, fever, tachycardia, rigors, headache, and vomiting.1
The effect of premedication on the risk or severity of infusion-related reactions has not been established; however, infusion-related reactions occurred less frequently in patients who received premedication compared with those who did not receive premedication (32 versus 42%) in the principal efficacy study.1 Because of the risk of infusion-related reactions, patients receiving mogamulizumab should receive a premedication regimen (e.g., diphenhydramine and acetaminophen) prior to the first infusion of mogamulizumab.1 If an infusion-related reaction occurs, a premedication regimen should be given prior to subsequent infusions of the drug.1
Patients should be closely monitored for manifestations of infusion-related reactions.1 In patients experiencing infusion-related reactions of any severity, the mogamulizumab infusion should be interrupted.1 For patients experiencing a grade 4 reaction, mogamulizumab therapy should be permanently discontinued.1 For patients experiencing a grade 1-3 reaction, the infusion may be restarted at a slower infusion rate once the reaction has completely resolved.1 Appropriate treatment and supportive care should be provided for infusion-related reactions of any severity.1 (See Infusion-related Reactions under Dosage: Therapy Interruption for Toxicity, in Dosage and Administration.)
Fatal and life-threatening infections (i.e., sepsis, pneumonia, cellulitis) have occurred in patients receiving mogamulizumab therapy.1, 3, 4 In the principal efficacy study, 18% of patients receiving mogamulizumab-kpkc developed a serious infectious complication or grade 3 or greater infection.1, 4
Reactivation of hepatitis B virus (HBV) infection also has been reported during postmarketing experience; however, the actual incidence of HBV infection and/or causal relationship to the drug have not been established.1, 4
Patients should be monitored for signs and symptoms of infection and prompt treatment should be instituted.1
Immune-mediated adverse events, sometimes fatal or life-threatening, have been reported in patients receiving mogamulizumab therapy.1, 7 Grade 3 or greater immune-mediated or possibly immune-mediated adverse events include myositis, myocarditis, polymyositis, hepatitis, pneumonitis, and a variant of Guillain Barré syndrome.1, 4
In the principal efficacy study, 1.9% of mogamulizumab-treated patients experiencing an immune-mediated adverse event (including one case of grade 2 polymyalgia rheumatica) received systemic immunosuppressive therapy.1 Grade 1 or 2 new-onset immune-mediated hypothyroidism was reported in 1.3% of patients receiving mogamulizumab-kpkc; management included observation or thyroid hormone replacement therapy (i.e., levothyroxine).1, 4, 11
If an immune-mediated adverse event is suspected, mogamulizumab therapy should be interrupted or permanently discontinued as appropriate.1, 4 Before initiating mogamulizumab therapy in patients with a history of autoimmune disease, clinicians should consider whether the benefit of mogamulizumab therapy outweighs the risks.1
Allogeneic Stem Cell Transplantation-related Complications
An increased risk of transplantation-related complications, including grade 3 or 4 acute graft-versus-host disease (GVHD), steroid-refractory GVHD, and death, have occurred in patients who underwent allogeneic stem cell transplantation following therapy with mogamulizumab.1, 4, 6, 10
Patients receiving mogamulizumab prior to allogeneic stem cell transplantation appear to be at greater risk of stem cell transplantation-related complications, particularly severe acute GVHD, when the drug is administered within a short time-frame (approximately 50 days) before hematopoietic stem cell transplantation (HSCT); therefore, some clinicians recommend delaying allogeneic stem cell transplantation until at least 50 days after the last dose of mogamulizumab.1, 4, 6, 10 Depletion of CC chemokine receptor 4 (CCR4)-positive T-cells following therapy with mogamulizumab in patients undergoing allogeneic stem cell transplantation may contribute to the increased risk of severe acute GVHD.6
Patients should be monitored closely for early manifestations of stem cell transplantation-related complications.1 Some clinicians also state that optimization of acute GVHD prophylaxis with antithymocyte globulin or post-transplantation cyclophosphamide should be considered.4
There is a potential for immunogenicity with mogamulizumab therapy.1 Development of anti-mogamulizumab antibodies was detected by electrochemiluminescence (ECL) in 10 of 258 patients (3.9%) receiving mogamulizumab-kpkc; none of the patients had evidence of neutralizing antibodies to the drug.1 No effects of antibody formation on pharmacokinetics, efficacy, or safety of the drug were observed.11
There are no available data regarding the risk of mogamulizumab use in pregnant women.1 In an animal reproduction study, no embryofetal toxic (i.e., spontaneous abortion, fetal death, fetal growth retardation) or teratogenic (i.e., external, visceral, or skeletal anomalies) effects were observed in monkeys receiving mogamulizumab-kpkc during organogenesis until delivery at exposure levels 27 times the human exposure at the recommended dosage.1
Immunoglobulin G (IgG) antibodies are known to cross the placenta during pregnancy.1 In an animal reproduction study in monkeys, mogamulizumab was detected in fetal plasma.1 Because mogamulizumab is an IgG antibody, mogamulizumab therapy is not recommended during pregnancy or in women of reproductive potential who are not using contraception.1
The manufacturer states that pregnancy status should be confirmed prior to initiation of mogamulizumab-kpkc in women of reproductive potential and that such women should be advised to use effective contraceptive methods while receiving mogamulizumab-kpkc and for at least 3 months following the last dose of the drug.1
It is not known whether mogamulizumab is distributed into human milk.1 The effects of the drug on nursing infants or on milk production also are unknown.1
The benefits of breast-feeding should be considered along with the importance of mogamulizumab to the woman and any potential adverse effects on the breast-fed infant from either the drug or the underlying maternal condition.1
Safety and efficacy of mogamulizumab have not been established in pediatric patients.1
In the principal efficacy study evaluating mogamulizumab-kpkc in patients with mycosis fungoides or Sézary syndrome, 51% of patients were 65 years of age or older.1 No overall differences in efficacy were observed between geriatric patients and younger adults, but some serious or grade 3 or greater adverse effects occurred more frequently in geriatric patients.1
Population pharmacokinetic analysis suggests that age (range of 22-101 years) has no effect on the pharmacokinetics, efficacy, or safety of mogamulizumab.1, 11 (See Dosage and Administration: Special Populations.)
Population pharmacokinetic analysis suggests that mild hepatic impairment (total bilirubin concentration not exceeding the upper limit of normal [ULN] with AST concentration less than the ULN or total bilirubin concentration exceeding the ULN, but not more than 1.5 times the ULN, with any AST concentration) and moderate hepatic impairment (total bilirubin concentration exceeding 1.5 times, but not more than 3 times ULN, with any AST concentration) have no effect on the pharmacokinetics, efficacy, or safety of mogamulizumab.1, 11
Pharmacokinetics of mogamulizumab has not been studied in patients with severe hepatic impairment (total bilirubin concentration exceeding 3 times the ULN with any AST concentration).1
Population pharmacokinetic analysis suggests that renal impairment (creatinine clearance less than 90 mL/minute) has no effect on the pharmacokinetics, efficacy, or safety of mogamulizumab.1, 11
Adverse effects reported in 20% or more of patients receiving mogamulizumab-kpkc include rash (including drug eruption), infusion-related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infections.1, 3
No formal drug interaction studies have been performed with mogamulizumab to date.1, 11 Drug interactions mediated by cytochrome P-450 (CYP) enzymes, other metabolizing enzymes, or transporters are not expected.11
Mogamulizumab, a defucosylated recombinant humanized anti-CC chemokine receptor 4 (anti-CCR4) monoclonal antibody, is an antineoplastic agent.1, 3, 10 The drug is an IgG1 kappa immunoglobulin.1, 3, 10, 11
Mogamulizumab binds selectively to CCR4, a chemokine receptor expressed on a subset of normal T-cells (e.g., regulatory T-cells) or at a high frequency in some malignant T-cells (e.g., cutaneous T-cell lymphoma [CTCL], adult T-cell leukemia/lymphoma [ATLL], peripheral T-cell lymphoma [PTCL]).1, 3, 8, 9, 11 CC chemokines play an important role in the regulation of lymphocyte migration to various organs, including the skin.1, 3, 10, 12 Following high-affinity binding of the defucosylated Fc region of mogamulizumab to the Fc receptor on CCR4, enhanced antibody-dependent cellular cytotoxicity results in depletion of target CCR4-expressing cells.1, 10, 11, 14
Mogamulizumab-kpkc exhibits dose-proportional pharmacokinetics over the dose range of 0.01-1 mg/kg.1 Following repeated doses of mogamulizumab-kpkc at the recommended dosage, steady-state concentrations are achieved after 12 weeks of therapy (i.e., 8 doses);1 systemic accumulation of the drug is 1.6-fold.1 The metabolic pathway of mogamulizumab has not been characterized.11 As a monoclonal antibody, the drug is expected to be degraded into small peptides and amino acids.11 The terminal half-life of mogamulizumab-kpkc is 17 days.1
Pharmacokinetics of mogamulizumab-kpkc do not appear to be affected by age (range: 22-101 years), sex, ethnicity, CTCL subtype (mycosis fungoides or Sézary syndrome), degree of CCR4 expression, or Eastern Cooperative Oncology Group (ECOG) performance status.1
Importance of instructing patients to read the manufacturer's patient information.1
Risk of dermatologic reactions.1 Importance of immediately informing clinician if new or worsening rash occurs.1
Risk of infusion-related reactions.1 Importance of immediately informing clinician if signs or symptoms of infusion-related reactions occur.1
Risk of infectious complications.1 Importance of informing clinician if signs or symptoms of infection (e.g., fever) occur.1
Risk of immune-mediated adverse effects.1 Importance of informing clinician of any history of autoimmune disorders.1
Risk of complications following allogeneic stem cell transplantation.1
Risk of fetal harm.1 Necessity of advising women of reproductive potential that they should use an effective method of contraception while receiving the drug and for at least 3 months after the last dose.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., autoimmune disorders).1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity. 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, for IV infusion | 4 mg/mL (20 mg) |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions March 9, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Kyowa Kirin. Poteligeo® (mogamulizumab-kpkc) injection for intravenous use prescribing information. Bedminster, NJ; 2018 Aug.
2. Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2019 Sep 23. [Web]
3. Kim YH, Bagot M, Pinter-Brown L et al. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol . 2018; 19:1192-1204. [PubMed 30100375]
4. Afifi S, Mohamed S, Zhao J et al. A drug safety evaluation of mogamulizumab for the treatment of cutaneous T-Cell lymphoma. Expert Opin Drug Saf . 2019; 18:769-776. [PubMed 31303060]
5. Suzuki Y, Saito M, Ishii T et al. Mogamulizumab Treatment Elicits Autoantibodies Attacking the Skin in Patients with Adult T-Cell Leukemia-Lymphoma. Clin Cancer Res . 2019; 25:4388-4399. [PubMed 31018922]
6. Sugio T, Kato K, Aoki T et al. Mogamulizumab Treatment Prior to Allogeneic Hematopoietic Stem Cell Transplantation Induces Severe Acute Graft-versus-Host Disease. Biol Blood Marrow Transplant . 2016; 22:1608-1614. [PubMed 27220263]
7. Bonnet P, Battistella M, Roelens M et al. Association of autoimmunity and long-term complete remission in patients with Sézary syndrome treated with mogamulizumab. Br J Dermatol . 2019; 180:419-420. [PubMed 30328116]
8. Geller S, Hollmann TJ, Horwitz SM et al. CCR4 expression in CD8+ cutaneous T-cell lymphomas and lymphoproliferative disorders and its implications for diagnosis and treatment. Histopathology . 2019; [PubMed 31355940]
9. Yonekura K, Kanzaki T, Gunshin K et al. Effect of anti-CCR4 monoclonal antibody (mogamulizumab) on adult T-cell leukemia-lymphoma: cutaneous adverse reactions may predict the prognosis. J Dermatol . 2014; 41:239-44. [PubMed 24628073]
10. Ollila TA, Sahin I, Olszewski AJ. Mogamulizumab: a new tool for management of cutaneous T-cell lymphoma. Onco Targets Ther . 2019; 12:1085-1094. [PubMed 30799938]
11. Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 761051Orig1s000: Multi-discipline review. From FDA website. [Web]
12. Solari R, Pease JE. Targeting chemokine receptors in disease--a case study of CCR4. Eur J Pharmacol . 2015; 763:169-77. [PubMed 25981299]
13. Kyowa Kirin. Poteligeo® (mogamulizumab-kpkc): dosing modifications for adverse reactions. Undated. Accessed 2019 Oct 23. [Web]
14. Duvic M, Evans M, Wang C. Mogamulizumab for the treatment of cutaneous T-cell lymphoma: recent advances and clinical potential. Ther Adv Hematol . 2016; 7:171-4. [PubMed 27247757]