Panoptic clinical review of the current and future treatment of relapsed/refractory T-cell lymphomas: Peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) tend to be aggressive and chemorefractory, with about 70% of patients developing relapsed/refractory disease. Prior to 2009, chemotherapies were the only options for relapsed/refractory PTCL, other than hematopoietic transplants. However, chemotherapy only improves survival by about 1 month compared with palliation. Four drugs are now approved in the US to treat relapsed/refractory PTCL: pralatrexate, romidepsin, belinostat, and brentuximab vedotin (for systemic anaplastic large cell lymphoma [sALCL]). Response rates with pralatrexate, romidepsin, and belinostat range from 25 to 54% in mixed relapsed/refractory PTCL populations, while 86% of sALCL patients respond to brentuximab vedotin. Here, we critically evaluate the evidence supporting the current drug treatment of relapsed/refractory PTCL, and look to the future to see how the treatment panorama may change with the advent of new targeted therapies, some of which (e.g., alisertib in PTCL and mogamulizumab in CCR4-positive adult T-cell leukemia/lymphoma) are already in phase 3 trials.

Panoptic clinical review of the current and future treatment of relapsed/refractory T-cell lymphomas: Cutaneous T-cell lymphomas.

Primary cutaneous T-cell lymphomas (CTCLs), such as mycosis fungoides and Sézary syndrome, are a rare group of non-Hodgkin lymphomas, usually treated using a multimodal approach. Unfortunately, many patients go on to develop relapsed/refractory disease. Systemic treatment for relapsed/refractory CTCL has historically relied on chemotherapies and interferons, and while active, responses are often short-lived. Three drugs are now approved in the US to treat relapsed/refractory CTCL including the oral retinoid, bexarotene, and histone deacetylase inhibitors, romidepsin and vorinostat. Although response rates are typically <35%, romidepsin and vorinostat can induce some durable responses in heavily pretreated patients and alleviate bothersome symptoms, such as pruritus. New studies indicate that the anti-CD30 antibody-drug conjugate brentuximab vedotin, anti-CCR4 antibody mogamulizumab, and fusion protein immunotoxin A-dmDT390-bisFv(UCHT1) may be particularly active in this setting. In this paper, we present an exhaustive review of the clinical data on current and possible future drug treatment options for relapsed/refractory CTCL.