Novel therapies for T cell lymphoma

Abstract

Peripheral T-cell lymphomas (PTCL) are a heterogeneous collection of lymphomas that are associated with a very poor prognosis. Conventional therapies, historically based on protocols for aggressive B-cell lymphomas, deliver less than adequate outcomes; the majority of patients experience early relapse after frontline treatment and current 5 year overall survival is only 10–30%. Clearly, new approaches are needed. In recent years there has been a plethora of novel agents showing activity in PTCL, often in patients with advanced relapsed or refractory disease. These agents include antifolate drugs (pralatrexate), histone deacetylase inhibitors (vorinostat, romidepsin, panobinostat, belinostat), nucleoside analogues (gemcitabine, forodesine, clofarabine), monoclonal antibodies (anti-CD52, anti-CD4, anti-CD2), immunotoxins (bentuximab vedotin; anti-CD30), fusion toxins (denileukin diftitox; CD25), immunomodulatory agents (IMiDs such as lenalidomide), and proteasome inhibitors (bortezomib). This is an exciting time in the treatment of PTCL, as our ever improving understanding of the distinguishing features, pathogenesis, molecular biology and progression of PTCL and the knowledge of the mechanism and efficacy of novel therapies, may see a real improvement in outcomes for patients. Biomarker co-development will be absolutely critical to advancing the field of PTCL therapy. Already, by dissecting out the biology of the disease, specific targeted approaches are being used (CD30, ALK, CCR4). Understanding the primary mechanism of action and key targets of the less specific agents such as the HDACi, lenalidome or aurora kinase inhibitors, will help us pre-select patients with the highest likelihood of benefit, reducing exposure to potential toxicities while reducing the overall health cost burden.