ORIGINAL RESEARCH article
Front. Immunol.
Sec. T Cell Biology
This article is part of the Research TopicEmerging Targeted and Immunotherapeutic Strategies in Oncology: From Solid Tumors to Hematologic MalignanciesView all 11 articles
Synergistic anti-tumor activity of the mTOR inhibitor everolimus and gemcitabine for relapsed/refractory peripheral T cell lymphoma
Provisionally accepted
- 1Guangdong Provincial People's Hospital, Guangzhou, China
- 2Sun Yat-sen University State Key Laboratory of Oncology in South China, Guangzhou, China
- 3Duke-NUS Medical School, Singapore, Singapore
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Background: Relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) patients face poor prognosis and limited therapies. The mTOR inhibitor everolimus and gemcitabine show modest efficacy as single agents in R/R PTCL, warranting investigation of combination regimens. Methods: This study conducted a single-center retrospective analysis of 24 patients diagnosed with peripheral T-cell lymphoma, aged 18 to 70 years, who experienced relapse or refractory disease following at least one first-line chemotherapy regimen, and received treatment at Guangdong Provincial People's Hospital between December 2017 and March 2021. CellTiter Glo and AnnexinV FITC/PI assays evaluated cell viability and apoptosis in vitro. Results: The combination showed significant efficacy: objective response rate (ORR) 70.8%, complete response (CR) rate 45.8%, median time to response 1.7 months. With median follow-up of 22.3 months (95% CI 5.7–39.0), median progression-free survival (PFS) was 9.9 months (95% CI 0–20.81), and median duration of response (DOR) 16.8 months. Patients with CR/partial response (PR) had longer PFS (18.7 vs. 1.2 months, P = 0.0007) and overall survival (OS) (30.9 vs. 5.8 months, P = 0.021) than those with stable/progressive disease. RNA-seq results showed that the combined therapeutic approach synergistically reduces cell viability and promotes apoptosis through the inhibition of the MYC signaling pathway. Conclusion: Everolimus-gemcitabine combination exhibits synergistic antitumor activity, offering a potential therapeutic strategy for R/R PTCL.
Keywords: Relapsed/refractory, peripheral T-cell lymphoma (PTCL), Everolimus, gemcitabine, Synergistic, anti-tumor activity
Received: 11 Aug 2025; Accepted: 29 Oct 2025.
Copyright: © 2025 Huang, Guo, Teng, Pang, Zhang, Sun, Ong, Tan and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wenyu Li, lwy80411@163.com
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