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Ferrata Storti Foundation
Haematologica 2021 Volume 106(12):3170-3175
Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma
Tiffany Tang,1 Peter Martin,2 Nagavalli Somasundaram,1 Cindy Lim,3 Miriam Tao,1 Eileen Poon,1 Maica J.D. Yunon,3 Shu Q. Toh,3 Sean X. Yan,4 Mohamad Farid,1 Jason Y. Chan1 and Soon T. Lim1
1Division of Medical Oncology, National Cancer Center Singapore, Singapore;
2Division of Medicine, Weill Cornell Medical College, New York, NY, USA; 3Division of Clinical Trials and Epidemiology, National Cancer Centre Singapore, Singapore and 4Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, Singapore
ABSTRACT
Selinexor is a selective inhibitor of nuclear export with anti-cancer properties. We performed a phase I study to determine the safety and maximum tolerated dose of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL). Patients with relapsed/refractory TCL and NKTL were treated with standard dose ICE, dexamethasone 20 mg on days 3 to 7, and escalating doses of oral selinexor on days 3, 5 and 7 in a 3+3 design. Dose levels (DL) 1, 2 and 3 were 40, 60 and 80 mg, respectively. Eleven patients with a median age of 60 years were enrolled; six at DL1 and five at DL2. Patients had received a median of two (range, 1-4) prior lines of treatment and seven had primary refractory disease at entry into the study. Patients received a median of three cycles (range, 1-6) of selinexor-DICE. The most common grade 1 or 2 toxicities included nau- sea (64%), fatigue (55%), and anorexia (45%) and the most common grade 3 or 4 toxicities included thrombocytopenia (82%), anemia (82%), neutropenia (73%), and hyponatremia (73%). Two patients developed dose-limiting toxicities at DL2 and one at DL1. Five patients discontin- ued treatment for reasons other than disease progression or lack of response. Of the ten evaluable patients, the overall and complete response rates were 91% and 82%, respectively. The maximum tolerat- ed dose of selinexor was 40 mg when combined with DICE. The com- bination showed promising complete response rates in patients with relapsed/refractory TCL and NKTL but was poorly tolerated. (clinicaltri- als.gov identifier: NCT03212937).
Introduction
T-cell lymphoma (TCL) is a heterogeneous group of non-Hodgkin lymphomas seen more commonly in Asia than in the West.1,2 The 5-year overall survival rates are approximately 30% for the most common subtypes of TCL, including periph- eral-T cell lymphoma (PTCL)-not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL) and natural-killer/T-cell lymphoma (NKTL).2 Patients with PTCL who relapse or progress after initial therapy have poor survival outcomes with median progression-free and overall survival of 3.1 and 5.5 months, respec- tively.3 However, patients who achieve a complete response to salvage therapy have better median progression-free and overall survival (12.2 and 18 months, respectively).3 Some patients who achieve a complete response to salvage therapy may be considered for high-dose chemotherapy (HDC) and autologous stem cell
Non-Hodgkin Lymphoma
Correspondence:
TIFFANY TANG
Tiffany.Tang.PL@gmail.com
Received: February 28, 2020. Accepted: October 7, 2020. Pre-published: November 5, 2020.
https://doi.org/10.3324/haematol.2020.251454 ©2021 Ferrata Storti Foundation
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