Selinexor With Anti-PD-1 Antibody as a Potentially Effective Regimen for Patients With Natural Killer/T-Cell Lymphoma Failing Prior L-Asparaginase and PD-1 Blockade

Author:

Tao Rong12ORCID,Liu Chuanxu12,Zhang Wenhao12,Zhu Yang1,Ma Yujie1,Hao Siguo1

Affiliation:

1. Department of Hematology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , People’s Republic of China

2. Department of Lymphoma, Fudan University Shanghai Cancer Center , Shanghai , People’s Republic of China

Abstract

Abstract Background Natural killer/T-cell lymphoma (NKTCL) is a rare and heterogeneous tumor type of non-Hodgkin’s lymphoma (NHL) with a poor clinical outcome. There is no standardized salvage treatment failing l-asparaginase-based regimens. Here we report our retrospective results of the combined use of selinexor and PD-1 blockade (tislelizumab) in 5 patients with NKTCL who had exhausted almost all available treatments. Patients and methods A total of 5 patients with relapsed/refractory(R/R) NK/T-cell lymphomas failing prior l-asparaginase and anti-PD-1 antibody were retrospectively collected. They were treated with at least one cycle of XPO1 inhibitor plus the same anti-PD-1 antibody. Anti-PD-1 antibody (Tislelizumab) was administrated at 200 mg on day 1 every 3 weeks and selinexor doses and schedules ranged from 40 mg weekly for 2 weeks per 21-day cycle to 60 mg weekly per cycle. Results Five patients with relapsed NKTCL with extensive organ involvement including 4 central nervous system (CNS) infiltration patients were included. Four patients achieved objective responses including 3 complete responses (CR) and 1 partial response (PR). After a median follow-up time of 14.5 (range, 5-22) months, 1 patient was still in remission with CR, and the other 4 patients discontinued due to disease progression with a median progression-free survival (PFS) of 6 months and median overall survival (OS) of 12 months. Four patients with CNS involvement achieved a median OS of 8 months. Our data suggest that selinexor in combination with an anti-PD-1 antibody is a promising small molecule and immunotherapy combination regimen for patients with relapsed or refractory NKTCL.

Funder

Shanghai Municipal Education Commission

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

Reference22 articles.

1. NK-/T-cell lymphomas;Wang,2021

2. Beyond first-line non-anthracycline-based chemotherapy for extranodal NK/T-cell lymphoma: clinical outcome and current perspectives on salvage therapy for patients after first relapse and progression of disease;Lim,2017 1

3. Expression of programmed cell death 1 and programmed cell death ligand 1 in extranodal NK/T-cell lymphoma, nasal type;Jo,2017

4. Selective inhibition of nuclear export with selinexor in patients with non-Hodgkin lymphoma;Kuruvilla,2017 15

5. The exportin-1 inhibitor selinexor exerts superior antitumor activity when combined with T-cell checkpoint inhibitors;Farren,2017

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