Peripheral T-cell lymphomas (PTCLs) are a rare, heterogeneous, and frequently aggressive family of malignancies, with 22 recognized subtypes. The evidence base for their treatment is limited and suffers from a dearth of prospective, randomized controlled clinical trials. But recently, the anti-CC chemokine receptor 4 (CCR4) antibody mogamulizumab (KW-0761) has offered a glimmer of hope against relapsed PTCLs and cutaneous T-cell lymphomas.

Of the 22 recognized subtypes of PTCLs, PTCL-not otherwise specified (NOS), antiimmunoblastic T-cell lymphoma (AITL), and anaplastic large-cell lymphoma (ALCL) are the most common, together representing 75% of cases.1 Survival rates are poor—particularly so for patients with PTCL-NOS and AITL, each of which is associated with a 5-year overall survival (OS) rate of 32%.1

Because PTCLs are rare and heterogeneous, the evidence base for their clinical management is very limited.

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Optimal induction therapy is unclear but patients are frequently treated with the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone).2,3 Efforts to intensify standard front-line chemotherapy and to use autologous hematopoietic stem cell transplantation (HSCT) do not appear to have improved patients’ survival rates.1-5

Patients with refractory or relapsed PTCL have very poor prognoses. Short of successful HSCT, for which many patients are not candidates, treatment is “usually palliative,” according to Nishitha Reddy, MD, and Bipin Savani, MD, both based at Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center in Nashville, TN.2

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In recent years, the US Food and Drug Administration (FDA) has approved pralatrexate and romidepsin for use with relapsed and refractory PTCL.2,4 Brentuximab vedotin is approved for relapsed and refractory ALCL.4

“These agents are quickly making their way toward upfront therapy in clinical trials,” noted Drs. Reddy and Savani. “Nevertheless, as a single drug, these agents are not curative. Combinations of these agents might be more efficacious and should be carefully evaluated in future studies.”

Meanwhile, however, a better understanding of surface receptor biology on PTCL cells has led to the development of new, still-investigational targeted agents, including the monoclonal antibodies alemtuzumab and mogamulizumab.5

Mogamulizumab targets the tumor CCR4, which is expressed on type 2 helper T cells, to induce receptor-dependent cytotoxicity.3,5 CCR4 is seen in up to 65% of PTCLs, and CCR4-positive PTCLs are associated with shorter survival times.3 It is infused intravenously weekly at 1.0 mg/kg.3,5

Results of a multicenter phase 2 clinical trial in Japan that indicate mogamulizumab is safe might represent a new treatment option for patients who face the grim prospect of relapsed CCR4-positive PTCL and cutaneous T-cell lymphomas (CTCLs).3 Although tumors’ CR4 expression levels did not predict overall response rates (ORRs), 13 (35%) of 37 study participants saw objective responses, including 5 patients (14%) for whom complete responses were reported.3 The median progression-free survival (PFS) was 3 months (95% CI, 1.6-4.9 months) overall, and OS was 14.2 months for patients with PTCL.3

Mogamulizumab-related adverse events included “reversible and manageable” grade 3/4 lymphocytopenia (81%/73%), neutropenia (38%/19%), and leukocytopenia (43%/14%); grade 2 or lower pyrexia was seen in 30% of patients.3 Grade 2 or higher lymphocytopenia was noted in 30 patients (81%) but “ultimately recovered to normal or baseline levels in all patients,” the authors noted.