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The following information helps you to find FDA Alerts and Pharmacist’s Applications to Practice quickly and easily. In cooperation with the Food and Drug Administration (FDA), and as a service to our members, HOPA periodically distributes information about newly approved therapies for cancer patients from FDA’s Office of Oncology Drug Products Director, Dr. Richard Pazdur to inform oncologists and professionals in oncology-related fields in a timely manner. Links to product labels will take you to relevant clinical information on the indication, contraindications, dosing, and safety. In sending this information, HOPA does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described.

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August 8, 2018, with PAP

https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761051s000lbl.pdf

On Aug. 8, 2018, the Food and Drug Administration approved mogamulizumab-kpkc (Poteligeo, Kyowa Kirin, Inc.) for adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy.

The approval of mogamulizumab-kpkc, a CC chemokine receptor type 4 (CCR4) directed monoclonal antibody, was based on a randomized, open-label, multicenter trial (Study 0761-010; NCT01728805) in patients with active MF or SS after at least one prior systemic therapy. Patients enrolled had a median of 3 prior therapies. The trial randomized 372 patients (44% with SS) to either mogamulizumab-kpkc or vorinostat.

Progression-free survival (PFS) was statistically significantly longer in the mogamulizumab-kpkc arm. The estimated median PFS was 7.6 months (95% CI: 5.6, 10.2) for those treated with mogamulizumab-kpkc compared with 3.1 months (95% CI: 2.8, 4.0) in the vorinostat arm (hazard ratio 0.53; 95% CI: 0.41, 0.69). The confirmed overall response rate was 28% and 5%, respectively (p<0.001).

The most common adverse reactions (reported in ≥20%) were rash, infusion-related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection. Serious adverse reactions occurred in 36% of patients, most often from infection (16% of all patients). The prescribing information includes warnings for dermatologic toxicity, infusion reactions, infections, autoimmune complications, and complications of allogeneic hematopoietic stem cell transplantation, including severe and refractory graft-versus-host disease.

The recommended mogamulizumab-kpkc dose is 1 mg/kg administered as an intravenous infusion over at least 60 minutes. Mogamulizumab-kpkc is administered on days 1, 8, 15, and 22 of the first 28-day cycle, then on days 1 and 15 of subsequent 28-day cycles until disease progression or unacceptable toxicity.

View full prescribing Information for Poteligeo.

FDA granted this application priority review, breakthrough therapy designation, and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).


Pharmacist’s Applications to Practice

Mogamulizumab-kpkc for Adults with Relapsed or Refractory Mycosis Fungoides or Sézary Syndrome After at Least One Prior Systemic Therapy

Author: Andrea Clarke, PharmD
PGY-2 Hematology/Oncology Pharmacy Resident
University of Minnesota Medical Center
Minneapolis, MN

What is the potential role for mogamulizumab in the treatment of mycosis fungoides or Sézary syndrome?

  • Mogamulizumab is a first-in-class defucosylated humanized IgG1 kappa monoclonal antibody that targets C-C chemokine receptor 4 (CCR4) expressed on the surface of tumor cells in T-cell malignancies, leading to antibody-dependent cellular cytotoxicity.1
  • The U.S. Food and Drug Administration (FDA) approval was based on a phase-3 multicenter randomized open-label trial (MAVORIC) of patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) who were assigned to mogamulizumab (n = 186) or vorinostat (n = 186), a histone deacetylase (HDAC) inhibitor that is FDA-approved for treatment of cutaneous T-cell lymphoma, with progression-free survival (PFS) as the primary end point.2
    • Mogamulizumab significantly improved investigator-assessed median PFS as compared to vorinostat, with 7.7 months vs. 3.1 months (hazard ratio [HR] 0.53, p < .0001). According to independent review, median PFS was 6.7 months vs. 3.8 months for mogamulizumab and vorinostat, respectively (HR 0.64, p < .0007).
    • Most common adverse events in the mogamulizumab group were infusion-related reactions (34%), diarrhea (24%), and drug eruption (24%), with the majority being grade 1 to 2 reactions.1,2
    • Grade 3 to 4 adverse event rates were 41% in each treatment arm. Drug rash was the most frequent cause of drug discontinuation (7%) in patients receiving mogamulizumab.1,2
    • Serious treatment-related adverse events were reported in 20% of patients receiving mogamulizumab, most frequently pyrexia (2%) and cellulitis (2%).1,2
  • The National Comprehensive Cancer Network added the use of mogamulizumab for the treatment of MF and SS as a category-2A recommendation in its guidelines published in August 2018. Other systemic therapies included in the same category are retinoids, interferons, HDAC inhibitors, extracorporeal photopheresis, low-dose methotrexate, and brentuximab vedotin.3

What role can the pharmacist play in the management of patients on mogamulizumab?

  • Mogamulizumab should be dosed at 1 mg/kg intravenously over at least 60 minutes on days 1, 8, 15, and 22 for the first 28-day cycle, and then on days 1 and 15 of subsequent cycles until the disease progresses or an unacceptable level of toxicity is reached.1
  • Monitor for infusion reactions, which usually occur during the first administration. Administer premedication with diphenhydramine and acetaminophen for the first infusion.1
    • Milder infusion reactions can be managed with infusion interruption, treatment of symptoms, and rate reduction by at least 50% upon resuming administration.
    • If a reaction occurs, administer premedication with diphenhydramine and acetaminophen for future infusions.1
  • Monitor for signs and symptoms of infection.1,2
  • Monitor for dermatologic toxicity to determine the need for dose modifications as provided in the package insert. Grade 1 rash can be managed with topical steroids, and grade 2–3 rash can be managed with dose delays and topical steroids.1
  • Monitor for immune-mediated complications, and consider the risks and benefits in patients with a history of autoimmune disease.1
  • For patients being considered for allogeneic hematopoietic stem cell transplantation, discuss increased risks of severe acute graft-versus-host-disease (GVHD), steroid-refractory GVHD, and transplant-related death in patients who receive mogamulizumab within approximately 50 days prior to transplant. Monitor patients for evidence of transplant-related complications.1,4
  • Uninsured patients may be eligible for patient assistance through Kyowa Kirin Cares. More information about patient assistance programs is available at https://www.poteligeohcp.com/.5

Clinical Pearls

  • Mogamulizumab is supplied in 20-mg/5-ml single-dose vials and should be stored under refrigeration in the original package to protect from light until time of use. They should not be shaken.1
  • For an infusion of mogamulizumab, a sterile, low protein binding, 0.22 micron in-line filter should be used.1
  • At the time of writing, this medication is not yet available, but availability is expected in the last quarter of 2018.

 
References

  1. Poteligio (mogamulizumab-kpkc) [package insert]. Bedminster, NJ: Kyowa Kirin, Inc.; August 2018.
  2. 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.
  3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. T-Cell Lymphomas (Version 5.2018). https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf. Accessed September 2, 2018.
  4. Fuji S, Inoue Y, Utsunomiya A, et al. Pretransplantation anti-CCR4 antibody mogamulizumab against adult T-cell leukemia/lymphoma is associated with significantly increased risks of severe and corticosteroid-refractory graft-versus-host disease, nonrelapse mortality, and overall mortality. J Clin Oncol. 2016;34:3426-3433.
  5. Kyowa Kirin Cares. Kyowa Kirin Cares Patient Assistance Program Application. Available at https://www.kyowakirincares.com/downloads/KyowaKirinCares_PAP_Application.pdf. Accessed September 18, 2018.
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