Mogamulizumab-kpkc (Poteligeo®) is a defucosylated humanized antibody directed against the chemokine receptor CCR4, which is overexpressed on malignant T cells. Mogamulizumab-kpkc (Poteligeo) was approved by the US Food and Drug Administration (FDA) for treatment of adult individuals with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy.
MF and SS are neoplasias of malignant T lymphocytes that usually possess the helper/inducer cell-surface phenotype. These kinds of neoplasms initially present as skin involvement and have been classified as cutaneous T-cell lymphomas. Cutaneous T-cell lymphomas differ from other T-cell lymphomas that involve the skin, such as anaplastic large cell lymphoma (CD30 positive), peripheral T-cell lymphoma (CD30 negative, with no epidermal involvement), adult T-cell leukemia/lymphoma (ATLL) (usually with systemic involvement), or subcutaneous panniculitic T-cell lymphoma.
ATLL is a mature T-cell neoplasm. Its causative agent has been confirmed to be long-term infection by human T-lymphotropic virus 1 (HTLV-1). A recent study demonstrated frequent expression of a chemokine receptor, CC chemokine receptor (CCR)-4. Various HTLV-1–associated inflammatory diseases are also commonly characterized by the infiltration of HTLV-1 T cells into target organs.
Mogamulizumab-kpkc (Poteligeo) is a CCR4-directed monoclonal antibody indicated for the treatment of adult individuals with relapsed or refractory MF or SS after at least one prior systemic therapy. Prior to its approval, treatment options consisted of retinoids (bexarotene, all-trans retinoic acid isotretinoin), interferons (IFN-alpha, IFN-gamma), histone deacetylase (HDAC) inhibitors (vorinostat, romidepsin), methotrexate, brentuximab vedotin, doxorubicin, gemcitabine, etoposide, chlorambucil, pentostatin, cyclophosphamide, temozolomide, bortezomib, pembrolizumab, or low-dose pralatrexate.
PEER-REVIEWED LITERATURE
SUMMARY
The MAVORIC study was an open-label, international, phase 3, randomized controlled trial. Between Dec 12, 2012, and Jan 29, 2016, 372 eligible individuals with relapsed or refractory MF or SS were randomly assigned at 61 medical centers. Eligible individuals were aged at least 18 years (in Japan, ≥20 years), had failed (for progression or toxicity as assessed by the principal investigator) at least one previous systemic therapy, and had an Eastern Cooperative Oncology Group performance score of 1 or less and adequate hematological, hepatic, and renal function. Individuals were randomly assigned (1:1) using an interactive voice web response system to mogamulizumab-kpkc (Poteligeo; 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 (400 mg daily). Stratification was by cutaneous T-cell lymphoma subtype (MF vs SS) and disease stage (IB–II vs III–IV). The primary endpoint was progression-free survival by investigator assessment in the intention-to-treat population. Individuals who received one or more doses of study drug were included in the safety analyses. Mogamulizumab-kpkc (Poteligeo) therapy resulted in superior progression-free survival compared with vorinostat therapy (median, 7.7 months [95% CI, 5.7–10.3] in the mogamulizumab-kpkc (Poteligeo) group versus 3.1 months [2.9–4.1] in the vorinostat group; hazard ratio, 0.53, 95% CI, 0.41–0.69; stratified log-rank P<0.0001).
OFF-LABEL INDICATION
There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
