Abstract

Abstract 2730

Introduction:

Recently, L-asparaginase-based combination chemotherapy was found to be effective in salvage treatment in patients with relapsed or refractory extranodal NK/T-cell lymphoma, nasal type. To explore the single-agent activity of L-asparaginase, we conducted a single-institute, prospective phase II study.

Methods:

Patients with relapsed or refractory extranodal NK/T-cell lymphoma, nasal type were eligible for enrollment regardless of prior treatment. L-asparaginase monotherapy (6000 U/m2 on days 1 to 7) was administered as the protocol treatment and repeated every 3 weeks for at most 8 cycles. For responding patients, the decision to proceed with hematopoietic stem-cell transplantation was made at the discretion of treating physicians. The primary endpoint was the best objective response after L-asparaginase.

Results:

A total of 40 patients were enrolled and treated with L-asparaginase for a median of 5 cycles (range, 1 – 8). The patient characteristics were shown in Table 1. Half of the patients had stage IV disease at enrollment and the vast majority (18 patients) presented with disseminated cutaneous and soft-tissue involvement. Thirty-seven patients (92.5%) had prior exposure to systemic chemotherapy and 14 of them (37.8%) received more than 1 line. The overall response rate was 82.5%. The complete response (CR) and partial response (PR) rates were 40% and 42.5%, respectively. The incidence of adverse events was shown in Table 2. In short, anemia, neutropenia, hypoalbuminemia, nausea and liver-related disorders were common toxicities, which were usually mild and manageable. No grade 4 adverse events and treatment-related mortality were observed. Five patients (12.5%) developed allergic reaction to L-asparaginase and 3 of them had to withdraw from the study since L-asparaginase re-challenge with prophylactic antiallergic agents was unsuccessful. After a median follow-up time of 31.6 months (range, 21.9 – 41.3), the median progression-free survival (PFS) was 12.8 months and median overall survival (OS) was not reached. Response status (CR, PR or no response) after L-asparaginase had a significant impact on either PFS (Figure 1) or OS (Figure 2). Moreover, its prognostic value was confirmed in the multivariate analysis.

Conclusions:

L-asparaginase demonstrated a high single-agent activity in salvage setting for patients with extranodal NK/T-cell lymphoma, nasal type. The first-line L-asparaginase-containing chemotherapy regimen warrants urgent investigation.

Table 1.

Patient Characteristics

 No. 
Total number 40 100 
Median age (years, range) 51 (32–69)  
Gender   
Male 26 65 
Female 14 35 
Performance status   
7.5 
36 90 
2.5 
B symptoms   
Yes 18 45 
No 22 55 
Lactate dehydrogenase   
Elevated 13 32.5 
Normal 27 67.5 
Primary site at first diagnosis   
    Upper aerodigestive tract 31 77.5 
    Non- upper aerodigestive tract 22.5 
Stage at enrollment   
    IE 12 30 
    IIE 17.5 
    IIIE 2.5 
IV 20 50 
International Prognostic Index   
    0–1 28 70 
    2 20 
    3 10 
Korean Prognostic Index   
    0 10 
    1 18 45 
    2 13 32.5 
    3–4 12.5 
Prior treatment   
    Radiotherapy alone 7.5 
    Chemotherapy alone 22.5 
    Chemotherapy and radiotherapy 28 70 
Disease status   
Relapsed 16 40 
Refractory 24 60 
 No. 
Total number 40 100 
Median age (years, range) 51 (32–69)  
Gender   
Male 26 65 
Female 14 35 
Performance status   
7.5 
36 90 
2.5 
B symptoms   
Yes 18 45 
No 22 55 
Lactate dehydrogenase   
Elevated 13 32.5 
Normal 27 67.5 
Primary site at first diagnosis   
    Upper aerodigestive tract 31 77.5 
    Non- upper aerodigestive tract 22.5 
Stage at enrollment   
    IE 12 30 
    IIE 17.5 
    IIIE 2.5 
IV 20 50 
International Prognostic Index   
    0–1 28 70 
    2 20 
    3 10 
Korean Prognostic Index   
    0 10 
    1 18 45 
    2 13 32.5 
    3–4 12.5 
Prior treatment   
    Radiotherapy alone 7.5 
    Chemotherapy alone 22.5 
    Chemotherapy and radiotherapy 28 70 
Disease status   
Relapsed 16 40 
Refractory 24 60 
Table 2.

Incidence of Adverse Events

 Any Grade (%) Grade 3 (%) Grade 4 (%) 
Hematologic    
Anemia 90 
Neutropenia 75 15 
Thrombocytopenia 7.5 
Nonhematologic    
Allergic reaction 12.5 
Hyperbilirubinemia 32.5 
ALT elevation 35 
AST elevation 27.5 
AKP elevation 30 
GGT elevation 32.5 2.5 
Hypoalbuminemia 85 
Hyperamylasemia 7.5 
Hyperglycemia 15 
Hyponatremia 15 
Hypokalemia 12.5 
Hypomagnesemia 10 
Nausea 50 
Vomiting 17.5 
Diarrhea 10 2.5 
Constipation 
Mucositis 
Headache 2.5 
Sensory neuropathy 2.5 
 Any Grade (%) Grade 3 (%) Grade 4 (%) 
Hematologic    
Anemia 90 
Neutropenia 75 15 
Thrombocytopenia 7.5 
Nonhematologic    
Allergic reaction 12.5 
Hyperbilirubinemia 32.5 
ALT elevation 35 
AST elevation 27.5 
AKP elevation 30 
GGT elevation 32.5 2.5 
Hypoalbuminemia 85 
Hyperamylasemia 7.5 
Hyperglycemia 15 
Hyponatremia 15 
Hypokalemia 12.5 
Hypomagnesemia 10 
Nausea 50 
Vomiting 17.5 
Diarrhea 10 2.5 
Constipation 
Mucositis 
Headache 2.5 
Sensory neuropathy 2.5 

ALT: alanine aminotransferase; AST: aspartate aminotransferase; AKP: alkaline phosphatase; GGT: gamma-glutamyl transpeptidase

Disclosures:

Off Label Use: L-asparaginase, which was used in our study for NK/T-cell lymphoma, is approved to treat acute lymphocytic leukemia by US and Chinese FDA.

Author notes

*

Asterisk with author names denotes non-ASH members.