Medical Research: What is the background for this study? What are the main findings?
Dr. Goh: Relapsed or refractory peripheral T-cell lymphoma after conventional chemotherapy is associated with a very poor prognosis and there is currently no recommendation on the standard approach to helping these patients. Novel targeted treatments for relapsed or refractory peripheral T-cell lymphoma such as romidepsin, pralatrexate, belinostat, and brentuximab vedotin has been approved by the US Food and Drug Administration (FDA) based on the results of their Phase II studies. With the exception of the remarkable efficacy of brentuximab vedotin in systemic anaplastic large cell lymphoma (86% of patients responding to treatment), the efficacy of romidepsin, pralatrexate, and belinostat in relapsed or refractory peripheral T-cell lymphoma is only modest with objective response rates between 25% and 29%. To our knowledge, no other clinical study has reported on the use of novel combination of targeted agents in in relapsed or refractory peripheral T-cell lymphoma. In our study, Of 23 patients assessable for responses, 10 (43%, 95% CI 23–63) patients had an objective response, of which 5 were complete responses. The combined proteasome and histone deacetylase inhibitor treatment shows promising activity for patients with peripheral T-cell lymphoma.
Medical Research: What should clinicians and patients take away from your report?
Dr. Goh: Peripheral T-cell lymphoma is clinically heterogeneous and associated with a very poor prognosis. There is an unmet need to improve the effectiveness of currently approved novel agents to induce remission and reduce disease burden to enable stem-cell transplantation. Our data compare favorably with the modest single-agent activities of novel targeted compounds and ours is the first study to show that the combination of two novel agents is safe, feasible, and promising in peripheral T-cell lymphoma. Our findings validate data from abundant preclinical studies suggesting that a combination approach is synergistic.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Goh: The identification of synergistic novel combinations pre-clinically and the translation to clinical studies represents the most rational way forward in harnessing the full potential of novel agents in peripheral T-cell lymphoma. This approach will certainly fill the emergent need for improved treatment strategies in these patients. Studies involving larger pools of patients would be required for further validation of the efficacy of proteasome and histone deacetylase inhibitor combination treatment for peripheral T-cell lymphoma patients. Optimum dosing schedules and dose combinations of various proteasome and histone deacetylase inhibitors combinations should be explored to further harness the full potential of such novel agents in peripheral T-cell lymphoma .
Dr Yeow Tee Goh MBBS (2015). Combination Targeted Therapy Promising For Difficult Peripheral T-Cell Lymphoma