MLN8237 ( alisertib ) and its role in peripheral T-cell lymphoma

Peripheral T-cell lymphomas (PTCL) are a diverse group of rare non-Hodgkin lymphomas (NHL) that carry a poor prognosis and are in need of effective therapies. A greater understanding of how these tumours proliferate as well as how best to exploit these processes should lead to more durable tumour regression and better clinical outcomes for patients. New approaches include the histone deacetylase inhibitors, antifolates, fusion proteins, nucleoside analogues and agents targeting the immune system, which are being investigated either as single agents or as a combination.

The authors review the evidence for the orally administered aurora A kinase inhibitor MLN8237 ( alisertib ) in T-cell lymphoma. No significant association between clinical response and AAK expression has been observed but inhibition of this enzyme in a Phase II study has demonstrated tumour regression in 27% of heavily pretreated B- and T-cell NHL, with 50% of PTCL patients responding and 3 of 4 patients achieving durable responses.

A Phase III trial in relapsed PTCL is recruiting patients comparing MLN8237 against single agent comparators. With regards to the data; the response rate of MLN8237 in refractory NHL is promising. The authors believe that further preclinical work identifying the best combinations to take through into clinical trials is important, particularly as this agent is used in earlier lines of therapy.