U.S. Food and Drug Administration (FDA)-Approved Indications

Compendial Uses

Poteligeo is a humanized monoclonal antibody (mAb) that binds to a protein (called CC chemokine receptor type 4 or CCR4) which is frequently expressed on leukemic cells of certain blood cancers including CTCL. Non-clinical in vitro studies demonstrate mogamulizumab-kpkc binding targets a cell for antibody-dependent cellular cytotoxicity (ADCC) resulting in depletion of the target cells. CCR4 is expressed on the surface of some Tcell malignancies and is expressed on regulatory T-cells (Treg) and a subset of Th2 T-cells (FDA, 2018; Kyowa Kirin, 2018).

The most common side effects (greater than or equal to 20%) of treatment included rash, infusion-related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection.

Labeled warning and precautions include complications of allogeneic HSCT after Poteligeo. It is recommended to monitor for severe acute graft-versus-host disease (GVHD) and steroid-refractory GVHD. Transplant-related mortality has occurred. In addition, patients should permanently discontinue Poteligeo for life-threatening (Grade 4) infusion reaction, rash, or for any Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). If moderate or severe (Grades 2 or 3) rash occurs, interrupt Poteligeo and administer at least 2 weeks of topical corticosteroids. If rash improves to Grade 1 or less, Poteligeo may be resumed. If mild (Grade 1) rash occurs, consider topical corticosteroids (Kyowa Kirin, 2018).

Mycosis Fungoides and Sézary Syndrome

Mycosis fungoides (MF) and Sézary syndrome (SS) are rare, hard-to-treat types of cutaneous T-cell lymphoma (CTCL), a type of non-Hodgkin lymphoma, in which lymphocytes become cancerous and affect the skin. MF accounts for about half of all lymphomas arising from the skin. In MF, symptoms can manifest in various stages, from papules, patches or erythematous pruritic plaques to lymph node, blood, and/or visceral involvement. Advanced stages can present with extracutaenous disease or advanced skin lesions (e.g., tumors). Unlike in MF, people with SS do not usually evolve through patches and plaques to erythroderma, but tend to present with diffuse skin involvement. SS is characterized by a widespread pruritic erythema and lymphadenopathy. The presence of cancerous T cells (called Sezary cells) are found in the skin, lymph nodes, and blood, and has the potential to spread to other organs in the body, including the liver, spleen, and bone marrow. It is not known if Sézary syndrome is an advanced form of mycosis fungoides or a separate disease. In either case, both MF and SS are defined histologically and staged by the same criteria (FDA, 2018; Hodak and Amitay-Laish, 2023; Hoppe et al., 2023; Kyowa Kirin, 2018; NCI, 2017; NIH, 2018; Rook and Olsen, 2023).

The tumor cells in SS “appear to be derived from skin homing CD4 positive T cells or central memory T cells that typically express cutaneous lymphocyte antigen (CLA) and high levels of the chemokine receptors CCR4 and CCR7” (Rook and Olsen, 2023).

On August 8, 2018, Kyowa Kirin Ltd, along with the U.S. Food and Drug Administration (FDA), announced the approval of Poteligeo (mogamulizumab-kpkc) injection, an anti-CCR4 monoclonal antibody, for intravenous use for the treatment of adults (18 years of age and older) with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy.

FDA approval was based on the Phase 3, open-label, multi-center, randomized MAVORIC (Mogamulizumab anti-CCR4 Antibody Versus ComparatOR In CTCL) trial which was conducted in the U.S., Europe, Japan and Australia. A total of 372 subjects with relapsed MF or SS were randomized to either receive mogamulizumab or vorinostat, a type of chemotherapy. Eligible subjects were aged at least 18 years (in Japan, greater than or equal to 20 years), had failed (for progression or toxicity) at least one previous systemic therapy (e.g., MTX, retinoids, interferons, histone deacetylase inhibitors (e.g., vorinostat (Zolinza) and romidepsin (Istodax)), brentuximab vedotin (Adcetris), or cytotoxic chemotherapeutic drugs) and had an Eastern Cooperative Oncology Group performance score of 1 or less and adequate hematological, hepatic, and renal function. Psoralen plus ultraviolet light therapy (PUVA) was not considered to be a systemic therapy. Subjects previously treated with anti-CD4 antibody or alemtuzumab were eligible provided their CD4+ cell counts are greater than or equal to 200/mm3. Subjects were randomly assigned (1:1) to mogamulizumab (n=186; 1 mg/kg intravenously on a weekly basis for the first 28-day cycle, then on days 1 and 15 of subsequent cycles) or vorinostat (n=186; 400 mg PO daily). Stratification was by cutaneous T-cell lymphoma subtype (mycosis fungoides vs Sézary syndrome) and disease stage (IB-II vs III-IV). The primary endpoint was progression-free survival by investigator assessment in the intention-to-treat population. The results showed that mogamulizumab demonstrated significantly superior progression-free survival (PFS) at a median of 7.6 months [95% CI: 5.6, 10.2] compared to 3.1 months with vorinostat [95% CI: 2.8, 4.0], [p<0.001]. The confirmed overall response rate for mogamulizumab and vorinostat was 28% and 5%, respectively (p<0.001). The authors concluded that mogamulizumab significantly prolonged progression-free survival compared with vorinostat, and could provide a new, effective treatment for patients with mycosis fungoides and, importantly, for Sézary syndrome, a subtype that represents a major therapeutic challenge in cutaneous T-cell lymphoma. This study is ongoing; however, enrollment is complete. (ClinicalTrials.gov, number NCT01728805) (Kim et al., 2018).

Combined Mogamulizumab and Total Skin Electron Beam Therapy for the Treatment of Mycosis Fungoides and Sezary Syndrome

Fong and colleagues (2020) stated that management of patients with refractory MF and SS is often challenging, as available treatments lack durable response and consistent activity across disease compartments. Combining low-dose total skin electron beam therapy (LD-TSEBT) upfront with mogamulizumab could optimize the clinical outcome of these patients. LD-TSEBT is effective in clearing skin disease, and mogamulizumab is an anti-tumor immunotherapy with long-term tolerability, suggesting its potential as a maintenance therapy after maximal response. These researchers examined the combination regimen in patients with SS who were previously treated. Two patients with SS were treated with combined mogamulizumab and LD-TSEBT. Both patients received mogamulizumab 1 mg/kg weekly × 4 and then bi-weekly; LD-TSEBT (12 Gy) was initiated within 2 days of starting mogamulizumab and given over 2 to 3 weeks. Safety and clinical response were examined. Mogamulizumab plus total skin electron beam therapy (Moga-TSE) was well-tolerated without any unanticipated adverse events (AEs). Patient 1 was a 63-year-old woman with 4 prior systemic therapies; time to global response with Moga-TSE was 9 weeks. Patient 2 was a 75-year-old man with 5 prior systemic therapies; time to global response was 4 weeks. Both patients lacked global response to their prior therapies but achieved global complete response (blood and skin) with Moga-TSE. After a follow-up of 72 weeks and 43 weeks, respectively, global complete response continued. The authors concluded that Moga-TSE demonstrated excellent tolerability and promising clinical activity with ongoing global complete responses in 2 patients with refractory SS. This encouraging experience supported their ongoing clinical trial examining the safety and effectiveness of Moga-TSE in patients with MF and SS. Moreover, these researchers stated that their phase-II clinical trial is underway with safety and efficacy endpoints.

Combined Mogamulizumab and Nivolumab for the Treatment of Solid Tumors

Combined Mogamulizumab and Bexarotene for the Treatment of Advanced Cutaneous T-Cell Lymphomas

Teoli et al (2022) stated that therapeutic options for patients with advanced-stage MF or SS who have failed 1st-line systemic therapies could be challenging, as several options are available. However, most evidence is based on observational and early phase studies due to the rarity of the disease. Mogamulizumab has recently been approved for the treatment of adult patients with MF or SS who have received at least 1 prior systemic therapy; it has a good tolerability profile prompting its use in combination with other agents. These investigators described the role of combined bexarotene and mogamulizumab in this setting. They described their experience with 4 MF/SS patients who failed 1st- and 2nd-line treatments and started the combination of mogamulizumab and bexarotene. The combination of bexarotene with mogamulizumab in patients with advanced MF/SS after the failure of bexarotene alone obtained a response in all 4 patients observed. The response was maintained longer than expected. The authors concluded that the combination mogamulizumab and bexarotene for the treatment of advanced-stage MF/SS is promising and deserves further investigation.

Criteria for Initial Approval

Aetna considers mogamulizumab-kpkc (Poteligeo) intravenous infusion medically necessary for the treatment of

of the following conditions:

Aetna considers all other indications as experimental and investigational.

Continuation of Therapy

Aetna considers continuation of mogamulizumab-kpkc (Poteligeo) therapy medically necessary for members with an indication listed in Section I when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Dosage and Administration

Poteligeo (mogamulizumab-kpkc) is available as 20 mg/5 mL (4 mg/mL) solution in a single-dose vial for injection.

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

Administer Poteligeo within 2 days of the scheduled dose. If a dose is missed, administer the next dose as soon as possible and resume dosing schedule.

Do not administer Poteligeo subcutaneously or by rapid intravenous administration.

Source: Kyowa Kirin, 2022