What is mogamulizumab-kpkc?
Mogamulizumab-kpkc is a first-in-class monoclonal antibody directed at the C-C chemokine receptor 4 (CCR4) expressed on the surface of regulatory T cell and Th2 cells.
Mogamulizumab-kpkc selectively binds to CCR4, a G protein-coupled receptor for chemokines involved in the movement of lymphocytes throughout the body. CCR4 is expressed on the surface of some T-cell malignancies and, through mogamulizumab-kpkc binding, results in antibody-dependent cellular cytotoxicity.
What is this approved for?
Mogamulizumab-kpkc is approved for patients with relapsed or refractory mycosis fungoides (MF) or Sezary syndrome (SS) after at least one prior systemic therapy.
What is the basis for this approval?
Mogamulizumab-kpkc was approved based on the results of MAVORIC, an open-label phase III, randomized trial in relapsed or refractory patients with MF or SS who had failed at least one prior systemic therapy. A total of 372 patients were randomized 1:1 to either mogamulizumab 1 mg/kg or vorinostat 400 mg and were stratified by disease subtype and stage. Tumor expression of CCR4 was not required for enrollment. Patients with CNS metastases and prior allogeneic transplant were excluded. The primary endpoint was progression-free survival (PFS) by investigators assessment with additional endpoints including overall response rate (ORR), duration of response, and quality of life.
PFS was significantly prolonged with administration of mogamulizumab, 7.7 months versus 3.1 months for vorinostat (HR 0.53; 95% CI 0.41-0.69, p<0.0001). ORR was 28 percent for mogamulizumab and 5 percent for vorinostat (risk ratio 23.1, 95% CI 12.8-33.1; p<0.0001) with the majority being partial responses. Main safety concerns for mogamulizumab were infusion reactions, rash, diarrhea, and fatigue. Response was not dependent on expression of CCR4 (Lancet Oncol 2018;19:1192-1204).
How do you administer this drug?
Mogamulizumab-kpkc is administered as an intravenous infusion with a 0.22 micron (or equivalent) in-line filter. It is given at a dose of 1 mg/kg over at least 60 minutes on days 1, 8, 15, and 22 of a 28-day cycle, then on days 1 and 15 of all subsequent 28-day cycles.
Are there any premedications needed?
Patients should receive diphenhydramine and acetaminophen prior to the first infusion. If an infusion reaction occurs, these should be repeated for all subsequent infusions as well as consideration for an extended infusion time.
What are the common side effects (> or =10%)?
* GI: mucositis, diarrhea, nausea, constipation
* Blood and lymphatic system disorders: thrombocytopenia, anemia
* Central nervous system: headache
* Vascular disorder: hypertension
* Respiratory: cough
* General: pyrexia, fatigue, edema
* Dermatologic: rash (drug eruption, dermatitis)
* Procedural complications: infusion-related reactions
* Infections: upper respiratory tract, skin
* Musculoskeletal: pain
What are the uncommon side effects (less than 10%)?
Additional side effects include hyperglycemia (9%), insomnia (9%), hyperuricemia (8%), dizziness (8%), peripheral neuropathy (7%), depression (7%), hypomagnesemia (6%), and arrhythmias (5%).
Are there any important drug interactions?
None currently studied.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
There are no known renal or hepatic dose adjustments; however, it has not been studied in severe renal or hepatic impairment.
Practical tips
* Median onset of a rash was 15 weeks. It may be treated with topical corticosteroids and drug interruption or discontinuation based on the grade of severity. A skin biopsy could be considered to distinguish between drug rash and progression of disease.
* Most infusion reactions occur during or shortly after the first infusion with the most commonly reported signs of chills, nausea, fever, tachycardia, rigors, headache, and vomiting.
* Immune-mediated reactions such as myocarditis, pneumonitis, hepatitis, myositis, and hypothyroidism have been reported and required treatment with immunosuppressants and therapy interruption/discontinuation.
What should patients know?
Patients should contact their health care provider if they experience any of the following: shortness of breath, new or worsening skin rash, and/or fever, sweats, or chills.
What else should I know about this drug?
* Patients may have an increased risk of transplant complications, including acute graft-versus-host disease (GVHD), steroid-refractory GVHD, and transplant-related death. Drug given ~50 days prior to transplant puts patients at higher risk.
* Effective contraception should be utilized during treatment and for at least 3 months after last dose.
What useful links are available?
* FDA approval announcement: https://bit.ly/2ZAETIb
* Indication and safety information: https://poteligeo.com/
Any ongoing clinical trials?
Clinical trials with mogamulizumab-kpkc are being conducted to investigate its place in therapy in other disease states and drug combinations. It is currently being studied alone for lymphoma or solid tumor malignancies, as well as in combination with docetaxel for non-small cell lung cancer, nivolumab for metastatic solid tumor malignancies, or pembrolizumab for relapsed or refractory lymphoma. More information is available about the clinical trials at https://clinicaltrials.gov.
KENDALL C. SHULTES, PHARMD, BCOP, is Assistant Professor at the Belmont University College of Pharmacy and Clinical Pharmacy Specialist at Vanderbilt-Ingram Cancer Center Cool Springs, Nashville, Tenn. JANELLE E. MANN, PHARMD, BCOP, is an Ambulatory Clinical Oncology Pharmacist, Washington University School of Medicine, Alvin J. Siteman Cancer Center, St. Louis, Mo., and serves as the Pharmacy Forum column editor. RAMASWAMY GOVINDAN, MD, Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, serves as the Pharmacy Forum column physician advisor.