Pharmacy Forum

Mogamulizumab-Kpkc (Poteligeo®) By Kendall C. Shultes, PharmD, BCOP

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

16 Oncology Times August 20, 2019