SIZE XSSIZE SMSIZE MDSIZE LG

You can also find additional information on FDA Alerts and Updates by listening to FDA Drug Safety Podcasts.

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.
xs
sm
md
lg