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Mogamulizumab-kpkc

Class: Antineoplastic Agents
- CC Chemokine Receptor 4 Antagonist
- CCR4 Inhibitor
Chemical Name: Anti-(human programmed CC chemokine receptor type 4) (human-mouse monoclonal KW-0761 heavy chain), disulfide with human-mouse monoclonal KW-0761 k-chain immunoglobulin G1 dimer
Molecular Formula: C6520H10072N1736O2020S42
CAS Number: 1159266-37-1
Brands: Poteligeo

Medically reviewed by Drugs.com. Last updated on Mar 9, 2020.

Introduction

Antineoplastic agent; recombinant humanized anti-CC chemokine receptor 4 (anti-CCR4) monoclonal antibody.1 3 10

Uses for Mogamulizumab-kpkc

Cutaneous T-cell Lymphoma (CTCL)

Mycosis Fungoides or Sézary Syndrome

Treatment of relapsed or refractory mycosis fungoides or Sézary syndrome that has progressed following at least 1 prior systemic therapy.1 3 Efficacy based on substantially prolonged progression-free survival and improved overall response rates compared with vorinostat.1 3

Designated an orphan drug by FDA for treatment of cutaneous T-cell lymphoma.2

Mogamulizumab-kpkc Dosage and Administration

General

  • Because of the risk of infusion-related reactions, a premedication regimen (e.g., acetaminophen and diphenhydramine) is recommended prior to the initial mogamulizumab infusion.1 If an infusion-related reaction occurs, administer premedication prior to subsequent infusions.1

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.1

Administer by IV infusion.1 Do not administer by sub-Q injection or rapid IV administration.1

Dilute mogamulizumab-kpkc injection to an appropriate concentration (see Dilution under Dosage and Administration) prior to IV infusion.1 (See Storage under Stability.)

Administer using a sterile, low-protein-binding 0.22-µm (or equivalent) inline filter.1

Do not mix with or administer simultaneously through the same IV line with other drugs.1

Dilution

Withdraw appropriate dose of mogamulizumab-kpkc injection containing 4 mg/mL from appropriate number of vials and inject 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

Mix the diluted solution by gentle inversion; do not shake.1

Immediate administration recommended.1 If necessary, may refrigerate diluted solution for ≤4 hours.1 (See Storage under Stability.)

Discard any partially used vials or diluted solution.1

Rate of Administration

Administer by IV infusion over ≥60 minutes.1

Dosage

Adults

Mycosis Fungoides or Sézary Syndrome
IV

Cycle 1: 1 mg/kg administered on days 1, 8, 15, and 22 of a 28-day cycle.1

Subsequent cycles: 1 mg/kg on days 1 and 15 of each 28-day cycle.1

Continue therapy until disease progression or unacceptable toxicity occurs.1

May administer within 2 days of scheduled dose.1 11 If a dose is missed, administer as soon as possible and then resume dosing schedule.1

Therapy Interruption for Toxicity
Dermatologic Toxicity
IV

If grade 2 or 3 rash occurs, interrupt therapy until the toxicity improves to grade 1 or less.1 May resume following completion of ≥2 weeks of topical corticosteroid therapy.1 (See Dermatologic Effects under Cautions.)

If Stevens-Johnson syndrome or toxic epidermal necrolysis is suspected, interrupt therapy until such diagnosis has been 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, permanently discontinue drug.1

Infusion-related Reactions
IV

If grade 1–3 infusion-related reactions occur, interrupt infusion and provide appropriate treatment.1 Upon resolution of the reaction, reduce the infusion rate by at least 50%.1 If reaction recurs and is unmanageable, discontinue drug.1 (See Infusion-related Reactions under Cautions.)

If grade 4 infusion-related reactions occur, permanently discontinue drug.1

Immune-mediated Events
IV

If an immune-mediated adverse effect is suspected, interrupt or permanently discontinue drug as appropriate.1 (See Immune-mediated Events under Cautions.)

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment: No dosage adjustment required.11 13 (See Hepatic Impairment under Cautions.)

Renal Impairment

No dosage adjustment required.11 13 (See Renal Impairment under Cautions.)

Geriatric Patients

Dosage adjustment based solely on age not required.11 (See Geriatric Use under Cautions.)

Cautions for Mogamulizumab-kpkc

Contraindications

  • No known contraindications.1

Warnings/Precautions

Dermatologic Effects

Rash (including drug eruption), sometimes fatal or life-threatening (i.e., Stevens-Johnson syndrome, toxic epidermal necrolysis), reported.1 3 4 5 9 10

Drug eruption most commonly presented as papular or maculopapular rash, lichenoid, spongiotic dermatitis, granulomatous dermatitis, or morbilliform rash; may also present as scaly plaques, pustular eruption, folliculitis, nonspecific dermatitis, or psoriasiform dermatitis.1 4 Median time to onset of drug eruption is 15 weeks; also may occur after 31 weeks of therapy.1

Monitor for skin reactions during therapy.1

Depending on nature and severity of rash, temporarily withhold or discontinue mogamulizumab therapy.1 (See Therapy Interruption for Toxicity under Dosage and Administration.) If grade 1 rash occurs, consider topical corticosteroid therapy.1 If grade 2 or 3 rash occurs, initiate topical corticosteroid therapy and continue for ≥2 weeks.1

Consider skin biopsy to distinguish drug eruption from disease progression.1 9 13

Infusion-related Reactions

Risk of infusion-related reactions (e.g., chills, nausea, fever, tachycardia, rigors, headache, vomiting), sometimes fatal or life-threatening.1 Generally occur more frequently during or shortly after first infusion than during subsequent infusions of the drug.1

Premedication (e.g., diphenhydramine and acetaminophen) recommended prior to first infusion.1 If an infusion-related reaction occurs, administer premedication prior to subsequent infusions.1

Monitor patients closely for manifestations of infusion-related reactions.1

Interrupt the infusion if an infusion-related reaction of any severity occurs.1 (See Therapy Interruption for Toxicity under Dosage and Administration.) Provide appropriate treatment and supportive care.1

Infectious Complications

Fatal and life-threatening infections (e.g., sepsis, pneumonia, cellulitis) reported.1 3 4

Reactivation of HBV infection reported during postmarketing experience.1 4

Monitor for signs and symptoms of infection and institute prompt treatment.1

Immune-mediated Events

Immune-mediated adverse events (e.g., myositis, myocarditis, polymyositis, hepatitis, pneumonitis, variant of Guillain Barré syndrome, polymyalgia rheumatica, hypothyroidism), sometimes fatal or life-threatening, reported.1 4 7

If an immune-mediated adverse event is suspected, interrupt or permanently discontinue drug.1 4 Consider potential benefits versus risks of the drug in patients with a history of autoimmune disease.1

Allogeneic Stem Cell Transplantation-related Complications

Increased risk of transplantation-related complications (i.e., grade 3 or 4 acute graft-versus-host disease [GVHD], steroid-refractory GVHD, death) in patients undergoing allogeneic stem cell transplantation following therapy with mogamulizumab.1 4 6 10

Risk of stem cell transplantation-related complications, particularly severe acute GVHD, increased in patients receiving the drug within a short time-frame (approximately 50 days) before allogeneic stem cell transplantation.1 4 Some clinicians recommend delaying allogeneic stem cell transplantation until ≥50 days after the last dose of mogamulizumab.4 10

Closely monitor for early manifestations of stem cell transplantation-related complications.1 Some clinicians recommend optimization of acute GVHD prophylaxis with antithymocyte globulin or post-transplantation cyclophosphamide.4

Immunogenicity

Potential for immunogenicity.1 Development of anti-mogamulizumab antibodies reported; neutralizing antibodies not detected.1 Effects on pharmacokinetics, efficacy, or safety of the drug not observed.11

Specific Populations

Pregnancy

No data in pregnant women; no embryofetal toxic or teratogenic effects demonstrated in animals.1

IgG antibodies are known to cross the placenta during pregnancy; in reproduction study in monkeys, mogamulizumab was detected in fetal plasma.1

Confirm pregnancy status prior to initiating mogamulizumab therapy.1 Not recommended during pregnancy or in women of reproductive potential who are not using contraception.1

Advise women of reproductive potential to use effective methods of contraception while receiving the drug and for ≥3 months after the last dose.1

Lactation

Not known whether mogamulizumab is distributed into human milk.1 Potential effects on nursing infants or on milk production not known.1

Consider benefits of breast-feeding along with mother's clinical need for mogamulizumab and any potential adverse effects of the drug or disease on the infant.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

No overall differences in efficacy observed between geriatric patients (≥65 years of age) compared with younger adults, but some serious or grade 3 or greater adverse effects occurred more frequently in geriatric patients.1

Hepatic Impairment

Pharmacokinetics, efficacy, and safety not affected by mild hepatic impairment (total bilirubin concentration not exceeding the ULN with AST concentration less than the ULN or total bilirubin concentration exceeding the ULN, but ≤1.5 times the ULN, with any AST concentration) or moderate hepatic impairment (total bilirubin concentration >1.5 times, but ≤3 times ULN, with any AST concentration).1 11

Pharmacokinetics not studied in patients with severe hepatic impairment (total bilirubin concentration >3 times the ULN with any AST concentration).1

Renal Impairment

Pharmacokinetics, efficacy, and safety not affected by renal impairment (Clcr <90 mL/minute).1 11

Common Adverse Effects

Rash (including drug eruption), infusion-related reactions, fatigue, diarrhea, musculoskeletal pain, upper respiratory tract infection.1

Interactions for Mogamulizumab-kpkc

No formal drug interaction studies to date.1 11 Drug interactions mediated by CYP enzymes, other metabolizing enzymes, or transporters not expected.11

Mogamulizumab-kpkc Pharmacokinetics

Absorption

Bioavailability

Dose-proportional pharmacokinetics over mogamulizumab-kpkc dose range of 0.01–1 mg/kg.1

Steady-state concentrations achieved after 12 weeks (i.e., 8 doses);1 systemic accumulation is 1.6-fold.1

Special Populations

Pharmacokinetics not affected by mild hepatic impairment (total bilirubin concentration not exceeding the ULN with AST concentration less than the ULN or total bilirubin concentration exceeding the ULN, but ≤1.5 times the ULN, with any AST concentration) or moderate hepatic impairment (total bilirubin concentration >1.5 times, but ≤3 times ULN, with any AST concentration).1

Pharmacokinetics not affected by renal impairment (Clcr <90 mL/minute).1 11

Age (range: 22–101 years), sex, ethnicity, CTCL subtype (mycosis fungoides or Sézary syndrome), degree of CCR4 expression, and Eastern Cooperative Oncology Group (ECOG) performance status do not affect pharmacokinetics.1

Distribution

Extent

Not known whether mogamulizumab is distributed into milk.1

IgG antibodies are known to cross placenta.1

Elimination

Metabolism

Metabolic pathway not characterized.11

Expected to be degraded into small peptides and amino acids.11

Half-life

17 days.1

Stability

Storage

Parenteral

Injection

Vials: 2–8°C in original carton to protect drug from light.1 Do not freeze.1

Diluted solution: Should be used immediately, but may be stored at 2–8°C for ≤4 hours after dilution.1 Do not freeze.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible

Sodium chloride 0.9%1

Actions

  • An IgG1 kappa immunoglobulin selective for CCR4, a chemokine receptor expressed on normal and malignant T-cells, including CTCL, adult T-cell leukemia/lymphoma (ATLL), and peripheral T-cell lymphoma (PTCL) cells.1 3 8 9 10 11

  • High-affinity binding of defucosylated Fc region of mogamulizumab to Fc receptor on CCR4 enhances antibody-dependent cellular cytotoxicity results in depletion of target CCR4-expressing cells.1 10 11 14

Advice to Patients

  • 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 childbearing potential that they should use an effective method of contraception while receiving the drug and for ≥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.)

Preparations

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.

Mogamulizumab-kpkc

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion

4 mg/mL (20 mg)

Poteligeo

Kyowa Kirin

AHFS DI Essentials™. © Copyright 2020, Selected Revisions March 9, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

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. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm

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. http://www.ncbi.nlm.nih.gov/pubmed/30100375?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/31303060?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/31018922?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/27220263?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/30328116?dopt=AbstractPlus

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; http://www.ncbi.nlm.nih.gov/pubmed/31355940?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/24628073?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/30799938?dopt=AbstractPlus

11. Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 761051Orig1s000: Multi-discipline review. From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/761051Orig1s000MultidisciplineR.pdf

12. Solari R, Pease JE. Targeting chemokine receptors in disease--a case study of CCR4. Eur J Pharmacol. 2015; 763:169-77. http://www.ncbi.nlm.nih.gov/pubmed/25981299?dopt=AbstractPlus

13. Kyowa Kirin. Poteligeo (mogamulizumab-kpkc): dosing modifications for adverse reactions. Undated. Accessed 2019 Oct 23. https://www.poteligeohcp.com/dosing/dosing-modifications.html

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. http://www.ncbi.nlm.nih.gov/pubmed/27247757?dopt=AbstractPlus

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