Efficacy and Safety Of Pegaspargase With Gemcitabine and Oxaliplatin In Patients With Treatment-naïve, Refractory Extranodal Natural Killer/T-Cell Lymphoma: A Single-Centre Experience
Authors: Gao Yan , Huang Hui-qiang , QiChun Cai , Wang XiaoXiao , Cai QinfQing , Xia Zhongjun , Bai Bing , Zhao Wei , Jiang Wenqi , Guan ZhongZhen 
Published: October 2019

Abstract

Purpose
Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive lymphoma with poor prognosis. The response rate to L-asperagenase(L-ASP) based multi-agent regimens is highly effective. Several clinical trials demonstraed good response and less toxicity for pegaspargase (PEG-ASP) in comparison to L-ASP. This is the first prospective study to evaluate the efficacy and safety of PEG-ASP combined with gemcitabine and oxaliplatin (PEG-ASP + Gemox) for patients with treatment-naïve and refractory or relapsed ENKTL.

Patients and methods
61 eligible patients treated by PEG-ASP + Gemox from March 2010 to March 2013 were analyzed. 36 newly -diagnosed patients and 25 refracrory/replased patients were enrolled, we also conducted extra matched-pair analysis between 20 stage IE/IIE cases selected from 36 newly -diagnosed patients in PEG-ASP + Gemox group and 18 stage IE/IIE patients in L-ASP + Gemox regimen group(unpublished data, Table 1,2). PEG-ASP + Gemox dosages were as follows: Gemcitabine 1000 mg/m2; day 1,8; oxaliplatin 130 mg/m2 day 1, PEG-ASP 2500 U/m2 im day1. The regimen was repeated every 3 weeks for a maximum of 6 cycles including 3 cycles induction chemotherapy for stage IE/IIE patients followed by involved-field radiotherapy. Furthermore autologous haematopoietic stem cell transplantation(AHSCT) was recommended to refractory/relapsed patients after achieved good response.

Results
55 patients were evaluable for response after a median 4 (1¨C6 ) cycles. The overall response(OR) rate was 90.9% (50/55), with a complete remission (CR) rate of 60.0% (33/55). After a median follow-up of 16.2 (4.0-39.5)months, the 1-, 2-year OS rates were 88.2%, 83.2%, and the 1-, 2- year PFS rates were all 85.2%. The median follow-up time was 19.6 (4.0-39.5)months for treatmen-naive patients. their OR, CR, partial remission(PR) rates were 94.0% (31/33), 66.7% (22/33), 27.3% (9/33), respectively. Both 1-, 2-year OS rates were 94.0%, 1-, 2-year PFS rates were all 93.9%. The median follow-up time was 18.7(4.5-36.2) months for refractory/replased patients. The OR and CR rates were 86.4% (19/22), 50.0% (11/22). The 1-, 2-year OS rates were 80.4% ,70.4%, the 1-, 2-year PFS rates were all 72.7%. Patients who achieved CR had undergone a median of two cycles (2¨C6). All patients received 187 cycles of chemotherapy, the incidence of rates of grade 1 and 2 adverse events were as follows: neutropenia, 69.6%; vomit 39.5%, transaminase elevation, 37.9%. Grade 3 and 4 adverse reactions were rare.

Conclusion
Our clinical trisl have demonstrated high efficacy and quick achievement of CR for the first time for PEG-ASP+Gemox regimen in the management of treatment-naïve and refractory/relapsed ENKTL patients. It also provided good chance of AHSCT as consolidation for chemosensitive patients. Meanwhile, PEG-ASP+Gemox regimen was conveniant and less toxic. Further investigation for PEG-ASP + Gemox regimen is warranted.

Disclosures:
No relevant conflicts of interest to declare.