On August 8, 2018, the CC chemokine receptor type 4 (CCR4)-directed monoclonal antibody mogamulizumab-kpkc (Poteligeo) was approved for adult patients with relapsed or refractory mycosis fungoides or Sézary syndrome after at least one prior systemic therapy.1,2
Supporting Efficacy Data
The current approval was based on progression-free survival findings in the open-label phase III MAVORIC trial, in which patients with active mycosis fungoides or Sézary syndrome after at least one prior systemic therapy were randomized to receive mogamulizumab-kpkc (1.0 mg/kg weekly for the first 28-day cycle and then on days 1 and 15 of subsequent cycles; n = 186) or vorinostat (Zolinza; 400 mg/d; n = 186).2,3 The median age of patients was 64 years; 44% of patients had Sézary syndrome; 58% were male; 70% were white; 38% had stage IB–II and 52% had stage IV disease; and the median number of prior systemic therapies was three. Patients treated with vorinostat were permitted to cross over to receive mogamulizumab-kpkc upon disease progression.
The median progression-free survival was 7.6 months in the mogamulizumab-kpkc group vs 3.1 months in the vorinostat group (hazard ratio = 0.53, P < .001) The confirmed overall response rate was 28% vs 5% (P < .001).
How It Works
Mogamulizumab-kpkc is a defucosylated humanized immunoglobulin G1 kappa monoclonal antibody that binds to CCR4, a G protein–coupled receptor for CC chemokines that is involved in the trafficking of lymphocytes to various organs. Studies in vitro have shown that mogamulizumab-kpkc binding targets cells for antibody-dependent cellular cytotoxicity, resulting in depletion of the target cells. CCR4 is expressed on the surface of some T-cell malignancies and is expressed on regulatory T cells and a subset of T helper 2 cells.
How It Is Used
The recommended mogamulizumab-kpkc dose is 1 mg/kg administered as an intravenous infusion over at least 60 minutes. It should be given on days 1, 8, 15, and 22 of the first 28-day cycle and then on days 1 and 15 of subsequent 28-day cycles until disease progression or unacceptable toxicity. Premedication with diphenhydramine and acetaminophen should be given for the first infusion.
Mogamulizumab-kpkc has warnings/precautions for dermatologic toxicity, infusion reactions, infections, autoimmune complications, and complications of allogeneic hematopoietic stem cell transplantation after mogamulizumab-kpkc treatment.
Dose modifications for dermatologic toxicity include permanent discontinuation for life-threatening (grade 4) rash or for any Stevens-Johnson syndrome or toxic epidermal necrolysis. For grade 2 or 3 rash, treatment should be interrupted and at least 2 weeks of topical corticosteroids given; mogamulizumab-kpkc can be resumed if rash improves to grade 1 or less. Topical steroids should be considered for grade 1 rash.
Treatment should be permanently discontinued for life-threatening (grade 4) infusion reactions. For grade 1 to 3 infusion reactions, infusion should be interrupted, and symptoms should be treated. After symptoms resolve, the infusion rate should be slowed by at least 50% when restarted; infusion should be discontinued if the reaction recurs and is not manageable. If an infusion reaction occurs, patients should receive premedication (eg, diphenhydramine and acetaminophen) for subsequent infusions.
The most common adverse events of any grade in patients receiving mogamulizumab-kpkc in the phase III trial (≥ 20% of patients) were rash including drug eruption, infusion-related reactions, fatigue, diarrhea, upper respiratory tract infection, and musculoskeletal pain. The most common grade ≥ 3 adverse event was rash including drug eruption (5%).
Serious adverse events occurred in 36% of patients treated with mogamulizumab-kpkc and most often involved infections (16%). Serious adverse events reported in more than 2% of patients were pneumonia (5%), sepsis (4%), pyrexia (4%), and skin infection (3%); other serious adverse events, each reported in 2% of patients, included hepatitis, pneumonitis, rash, infusion-related reaction, lower respiratory tract infection, and renal insufficiency. Adverse events led to treatment discontinuation in 18% of patients, with the most common cause being drug eruption (7%). Fatal adverse events within 90 days of the last dose occurred in 2.2% of patients who received mogamulizumab-kpkc as randomized or crossover treatment.
Fatal and life-threatening immune-mediated complications were reported in patients receiving mogamulizumab-kpkc. Grade ≥ 3 immune-mediated or possibly immune-mediated reactions include myositis, myocarditis, polymyositis, hepatitis, pneumonitis, and a variant of Guillain-Barré syndrome. Use of systemic immunosuppressants for immune-mediated reactions was reported in 1.9% of patients, including for a case of grade 2 polymyalgia rheumatica. New-onset hypothyroidism (grade 1 or 2) was reported in 1.3% of patients.
Mogamulizumab-kpkc has warnings/precautions for dermatologic toxicity, infusion reactions, infections, autoimmune complications, and complications of allogeneic hematopoietic stem cell transplantation (HSCT) after mogamulizumab-kpkc treatment. Patients should be monitored for infections and treated promptly. Treatment should be interrupted or permanently discontinued as appropriate for autoimmune complications. HSCT patients should be monitored for severe acute graft-vs-host disease and steroid-refractory graft-vs-host disease. Transplant-related mortality has occurred. ■
1. U.S. Food and Drug Administration: FDA approves mogamulizumab-kpkc for mycosis fungoides or Sézary syndrome. Available at www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm616180.htm. Accessed September 20, 2018.
2. Poteligeo (mogamulizumab-kpkc) injection prescribing information, Kyowa Kirin, Inc, August 2018. Available at www.accessdata.fda.gov/drugsatfda_docs/label/2018/761051s000lbl.pdf. Accessed September 20, 2018.
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 19:1192-1204. 2018.
Health-care professionals should report all serious adverse events suspected to be associated with the use of any medicine or device to FDA’s MedWatch Reporting System by completing a form online at www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178), by mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).