Denileukin Diftitox (Ontak) as Maintenance Therapy for Peripheral T-Cell Lymphomas: Three Cases with Sustained Remission.

Alejandra C Fuentes,Ellen Szwed,Nam H Dang,Cathy D Spears,Sandeep Thaper,Long H Dang

doi:10.1155/2015/123756

Abstract

Peripheral T-cell lymphomas (PTCL) are rare but markedly aggressive forms of non-Hodgkin's lymphoma (NHL). They carry a poor prognosis, with current therapeutic approach being generally ineffective. The most employed first-line treatment is CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), which still results in high rates of relapses. Denileukin diftitox is a fusion protein combining the cytotoxic portion of the diphtheria toxin and the receptor-binding domain of the interleukin-2 (IL-2) molecule, thereby targeting cells expressing the IL-2 receptor, including both T-cell and B-cell lymphomas. It has been approved for the treatment of cutaneous T-cell lymphomas, and it has documented activity in PTCL both as a single agent and as part of combination therapy. This report documents three cases of PTCL where denileukin diftitox has been used as long-term maintenance therapy after complete remission was achieved. While the overall survival rate of patients with advanced stage, refractory PTCL is generally poor (with median overall survival of 5.5 months), the three patients described in this report are all experiencing an ongoing complete remission for more than four years.

Highlights

Non-Hodgkin’s lymphomas (NHL) are a heterogeneous group of lymphoproliferative disorders
Only about 15–20% of NHL cases originate from the T-cell lineage, T-cell non-Hodgkin’s lymphomas are generally more aggressive and have a poorer prognosis than their B-cell counterpart, with decreased short-term survival and frequent relapses
In 2008 we reported the first case of prolonged remission with long-term maintenance therapy with Denileukin diftitox (DD) in a patient with advanced stage, relapsed/refractory Peripheral T-cell lymphomas (PTCL) [9]

Summary

Introduction

Non-Hodgkin’s lymphomas (NHL) are a heterogeneous group of lymphoproliferative disorders. Only about 15–20% of NHL cases originate from the T-cell lineage, T-cell non-Hodgkin’s lymphomas are generally more aggressive and have a poorer prognosis than their B-cell counterpart, with decreased short-term survival and frequent relapses. In 2008 we reported the first case of prolonged remission with long-term maintenance therapy with DD in a patient with advanced stage, relapsed/refractory PTCL [9]. This patient is presently experiencing an ongoing complete remission of more than 9 years (ND, personal communications). This current report describes three additional cases of patients with advanced stage PTCL in which DD was used successfully as long-term maintenance therapy to maintain ongoing remission, illustrating the exciting potential of this novel drug as an agent that can be used as maintenance therapy in selected cases of PTCL

Case 1

Case 2

Case 3

Findings

Discussion