Mogamulizumab

Uses

Mogamulizumab is a monoclonal antibody used to treat relapsed or refractory mycosis fungoides or Sézary syndrome after attempting one other therapy.

For the intravenous use for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy. This approval provides a new treatment option for patients with MF and is the first FDA approval of a drug specifically for Sézary Syndrome .

Mogamulizumab is also used to associated treatment for these conditions: Refractory Mycosis Fungoides/Sezary Syndrome, Relapsed Mycosis Fungoides/Sezary Syndrome

How Mogamulizumab works

Mogamulizumab selectively binds to and inhibits the activity of CCR4, which may block CCR4-mediated signal transduction pathways and, so, chemokine-mediated cellular migration and proliferation of T cells, as well as chemokine-mediated angiogenesis. Additionally, this agent may induce antibody-dependent cell-mediated cytotoxicity (ADCC) against CCR4-positive T cells. CCR4, a G-coupled-protein receptor for C-C chemokines such MIP-1, RANTES, TARC and MCP-1, is expressed on the surfaces of some types of T cells, endothelial cells, and certain types of neurons. CCR4, also known as CD194, may be overexpressed on adult T-cell lymphoma (ATL) and peripheral T-cell lymphoma (PTCL) cells . In addition to directly targeting malignant T cells expressing CCR4, mogamulizumab depletes Treg cells, an important therapeutic target in many human cancers because of their role in suppressing host antitumor immunity .

Toxicity

The most common adverse reactions (reported in ≥20% of patients randomized to mogamulizumab) were rash (including drug eruption), infusion-related reactions, fatigue, diarrhea, upper respiratory tract infection and musculoskeletal pain . Due to various adverse effects related to this drug, the adverse reactions have been categorized by organ system. Because of the risk of serious/fatal ADRs, patients administered mogamulizumab should be carefully monitored .

Upper respiratory tract infection: This may occur due to decreased immunity following the administration of this drug. Monitor for signs of respiratory infection including fever, cough and shortness of breath .

Dermatological: Patients must contact their healthcare provider immediately if they experience a new or worsening skin rash. Treatment should be temporarily interrupted for moderate or severe skin rashes and permanently discontinued for a life-threatening rash. Fatal and life-threatening skin adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have occurred in recipients of mogamulizumab. Rash (drug eruption) is one of the most common adverse reactions associated with mogamulizumab , .

Infusion Reactions: Patients must contact their healthcare provider immediately for signs or symptoms of infusion reactions. Treatment should be suspended for any infusion reaction and permanently discontinued for any life-threatening infusion reaction .

Infections: Patients must contact their healthcare provider if they experience fever or other signs of infection. Infections should be monitored and treated promptly .

Autoimmune Complications: Immune-mediated or possibly immune-mediated reactions have included myositis, myocarditis, polymyositis, hepatitis, pneumonitis, and a variant of Guillain- Barré syndrome . Patients must notify their healthcare provider of any history of autoimmune disease. Treatment should be suspended or permanently discontinued as appropriate . Fatal and life-threatening immune-mediated complications have been reported in recipients of this drug .

Musculoskeletal pain: This drug may cause musculoskeletal pain

A note on complications of allogeneic hematopoietic stem cell transplantation: Patients must be aware of the possible risk of post-transplant complications when taking this agent. Patients should be monitored for severe acute graft-versus-host disease (GVHD) and steroid-refractory GVHD.

Females of Reproductive Potential: Females who are able to become pregnant should use an effective method of birth control during treatment with Poteligeo and for at least three months after the last dose .

Food Interaction

Mogamulizumab Disease Interaction

Moderate: autoimmune disease

Volume of Distribution

The central volume of distribution is 3.6 L .

Elimination Route

Following repeated dosing of the approved recommended dosage, steady-state concentrations were reached after 8 doses (12 weeks), and the systemic accumulation was 1.6-fold. At steady state, the peak concentration (Cmax,ss) is 32 (68%) μg/mL, the trough concentration (Cmin,ss) is 11 (239%) μg/mL, and AUCss is 5577 (125%) μg•hr/mL .

Half Life

The terminal half-life is 17 days .

Clearance

Clearance is 12 mL/h .

Innovators Monograph

You find simplified version here Mogamulizumab