Asparaginase Treatment Patterns, Toxicity, and Outcomes Among Patients with Extranodal NK/T-Cell Lymphoma: A North American Multicenter Retrospective Cohort Study
Authors: Allen Pamela B. , Bagley Evan , Graf Kevin , Sethi Tarsheen , Foss Francine M. , Dong Ning , Saeed Hayder , Wang Jie , Dittus Christopher , Paulino Darina , Wilcox Ryan A. , Barta Stefan K. , Carvajal Veronica , Mehta-Shah Neha , Mou Eric , Ravindra Aditya , Haverkos Bradley M. , Mehta Amitkumar N. , Shea Lauren Kelly , Zain Jasmine , Reef Daniel K , Ayzman Ann , Greenwell Irl Brian 
Published: December 2024

Extranodal NK/T-cell Lymphoma (ENKTL) is a rare EBV associated lymphoma best characterized in Asian populations, with little data describing outcomes in North Americans. ENKTL has poor responses to traditional anthracycline-containing lymphoma regimens. Systemic agents such as asparaginase and gemcitabine, as well as radiation for localized disease, are considered important in improving outcomes. However, toxicity in older patients can be a limitation of therapy, especially with asparaginase based regimens. There is also no standard therapy for patients with ENKTL, especially those who may be older or have significant comorbidities. This analysis seeks to define treatment patterns and outcomes in for North American ENKTL patients with an emphasis on the impact of asparaginase use, including how asparaginase use and toxicity changes based on patient age.
A retrospective, multicenter database included patients ENKTL patients older than 18 years diagnosed between 2010 and 2022. Clinical, pathologic, treatment and survival characteristics were collected. Survival was analyzed using the Kaplan-Meier method. Cox proportional hazards regression will be used to assess the relationship of characteristics (eg asparaginase exposure) and outcome. Predictive variables with p &lt; 0.2 from the univariable analysis will be included in a multivariable analysis. All reported p values will be 2-sided, and the significance level will be at &lt;0.05. Analysis of outcomes with age will occur both as categorical variables (&lt;40yo, 40-60yo, 60+), and with age as a continues variable. Due to limited expected numbers, descriptive analysis of individuals will be provided for individuals 65+ and 70+.
134 patients from 8 academic institutions were included in the analysis. 42 (31.3%) patients were younger than 40 years old, 48 patients were between the ages of 40 - 60yo (35.8%), and 44 patients (32.8%) were 61 years and older. Eighty-four patients received asparaginase (ASP) and 50 did not (non-ASP).
Grade 3+ transaminase elevations (AST or ALT &gt;5x ULN) were common among pts receiving ASP seen in 23 of 84 patients (27%) versus those not receiving ASP (3 of 50, 6%). Lipase elevations were seen in 21 (25%) of asparaginase patients. Other notable toxicities in ASP vs non-ASP patients include hypertriglyceridemia (24% vs 0%), hypofibrinogenemia (24% vs 2%), neutropenic fever (20% vs 8%), hypersensitivity reactions (10% vs 2%), bleeding (8% vs 2%), VTE (5% vs 2%), and unplanned hospitalizations (31% vs 10%). In patients who received ASP, at least one AE was seen in 53% of patients &lt;40yo, 68% between 40-60yo, and 66% of patients 61 years and older. Therapy related deaths were seen in 7 of the 84 patients who received ASP (8%) and in 4 of 50 patients non-ASP patients (8%). ASP was discontinued due to toxicity in 24 patients (28%).
Overall (OR) and Complete (CR) response rates were 80% (62% CR) in the ASP group and 54% (46%) in the non-ASP groups. In patients &lt;40yo, OR (CR) rates were 82%(64%) vs 57%(42%) in ASP vs non-ASP groups. In patients aged 40-60yo, OR(CR) rates were 76%(62%) vs 52%(47%), and in patients 61+, OR(CR) rates were 81%(59%) vs 53%(47%) in ASP vs non-ASP groups. Interestingly, the higher response rates did not translate to a statistically significant advantage in overall survival (p=0.44), with difference in PFS approaching statistical significance at 0.077.
This analysis supports that ASP containing regimens have significant clinical activity in ENKTL, but are associated with significant rates of unique toxicities, resulting in discontinuation of ASP in a quarter of patients, but no increase in therapy associated death. The efficacy benefit as measured by response rates was maintained across age groups. We lacked statistical power to detect differences in survival, key subgroup analyses will be presented at the meeting in addition to other clinical, pathologic, and treatment variables. Additionally, we will discuss use of radiation, and more detailed characteristics of asparaginase dosing, and differences between chemotherapy backbones