Efficacy and Safety of a Pegasparaginase-Based Chemotherapy Regimen vs an L-asparaginase-Based Chemotherapy Regimen for Newly Diagnosed Advanced Extranodal Natural Killer/T-Cell Lymphoma: A Randomized Clinical Trial.

Abstract

Importance:

The L-asparaginase-based SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen has shown higher response rates and survival benefit over an anthracycline-containing regimen. However, the safety profile was not satisfied. A well-tolerated regimen with promising efficacy is lacking.

Objective:

To compare the efficacy and safety of the DDGP (dexamethasone, cisplatin, gemcitabine, and pegaspargase) regimen with the SMILE regimen in newly diagnosed advanced-stage (III/IV) extranodal natural killer/T-cell lymphoma (ENKL).

Design, Setting, and Participants:

This was an open-label, multicenter, randomized clinical trial that took place across 12 participating hospitals in China from January 2011 to February 2019. Patients were eligible if they were 14 to 70 years old with newly diagnosed ENKL in stages III/IV and had an Eastern Cooperative Oncology Group performance status of 0 to 2. Eligible patients were evenly randomized to either the DDGP or SMILE group.

Interventions:

Patients in each group were treated with the assigned regimen every 21 days for 6 cycles.

Main Outcomes and Measures:

The primary end point was progression-free survival (PFS), and secondary end points included overall response rate and overall survival (OS). The adverse events between the DDGP and SMILE groups were compared.

Results:

Among the 87 randomized patients, 80 received treatment (40 in the DDGP group and 40 in the SMILE group); the median (IQR) age was 43 (12) years, and 51 (64%) were male. The baseline characteristics were similar between the groups. At a median follow-up of 41.5 months, the median PFS was not reached in the DDGP group vs 6.8 months in the SMILE group (HR, 0.42; 95% CI, 0.23-0.77; P = .004), and the median OS was not reached in the DDGP group vs 75.2 months in the SMILE group (HR, 0.41; 95% CI, 0.19-0.89, P = .02). The PFS rate at 3 years and OS rate at 5 years were higher in the DDGP group vs the SMILE group (3-year PFS, 56.6% vs 41.8%; 5-year OS, 74.3% vs 51.7%). The overall response rate was higher in the DDGP group than in the SMILE group (90.0% vs 60.0%; P = .002). Grade 3 and 4 hematologic toxic effects were more frequently reported in the SMILE group vs the DDGP group (leukopenia, 85.0% vs 62.5%; neutropenia, 85.0% vs 65.0%).

Conclusions and Relevance:

In this randomized clinical trial, the DDGP regimen showed promising preliminary results for patients with newly diagnosed local advanced ENKL. A confirmation trial based on larger population is warranted.

Trial Registration:

ClinicalTrials.gov Identifier: NCT01501149.

• Authors: Xinhua Wang, Lei Zhang, Xiangli Liu, Xin Li, Ling Li, Xiaorui Fu, Zhenchang Sun, Jingjing Wu, Xudong Zhang, Jiaqin Yan, Yu Chang, Feifei Nan, Zhiyuan Zhou, Xiaolong Wu, Li Tian, Minrui Ma, Zhaoming Li, Hui Yu, Linan Zhu, Yingjun Wang, Cunzhen Shi, Xiaoyan Feng, Jiwei Li, Mengjie Ding, Jieming Zhang, Meng Dong, Hongwei Xue, Jinghua Wang, Liqun Zou, Liping Su, Jianqiu Wu, Lihong Liu, Huizheng Bao, Liling Zhang, Yanzhen Guo, Shuxia Guo, Yi Lu, Ken H Young, Wencai Li, Mingzhi Zhang
• Journal: JAMA oncology (JAMA Oncol) Vol. 8 Issue 7 Pg. 1035-1041 (07 01 2022) ISSN: 2374-2445 [Electronic] United States
• PMID: 35708709 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Dexamethasone
• Asparaginase

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Asparaginase (adverse effects, therapeutic use)
• Dexamethasone (adverse effects, therapeutic use)
• Female
• Humans
• Killer Cells, Natural (pathology)
• Lymphoma, Extranodal NK-T-Cell (drug therapy, pathology)
• Male
• Middle Aged