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   
0 3 7.5 
1 36 90 
2 1 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 9 22.5 
Stage at enrollment   
    IE 12 30 
    IIE 7 17.5 
    IIIE 1 2.5 
IV 20 50 
International Prognostic Index   
    0–1 28 70 
    2 8 20 
    3 4 10 
Korean Prognostic Index   
    0 4 10 
    1 18 45 
    2 13 32.5 
    3–4 5 12.5 
Prior treatment   
    Radiotherapy alone 3 7.5 
    Chemotherapy alone 9 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   
0 3 7.5 
1 36 90 
2 1 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 9 22.5 
Stage at enrollment   
    IE 12 30 
    IIE 7 17.5 
    IIIE 1 2.5 
IV 20 50 
International Prognostic Index   
    0–1 28 70 
    2 8 20 
    3 4 10 
Korean Prognostic Index   
    0 4 10 
    1 18 45 
    2 13 32.5 
    3–4 5 12.5 
Prior treatment   
    Radiotherapy alone 3 7.5 
    Chemotherapy alone 9 22.5 
    Chemotherapy and radiotherapy 28 70 
Disease status   
Relapsed 16 40 
Refractory 24 60 
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Table 2.

Incidence of Adverse Events

Any Grade (%)Grade 3 (%)Grade 4 (%)
Hematologic    
Anemia 90 5 0 
Neutropenia 75 15 0 
Thrombocytopenia 7.5 0 0 
Nonhematologic    
Allergic reaction 12.5 0 0 
Hyperbilirubinemia 32.5 0 0 
ALT elevation 35 0 0 
AST elevation 27.5 0 0 
AKP elevation 30 0 0 
GGT elevation 32.5 2.5 0 
Hypoalbuminemia 85 0 0 
Hyperamylasemia 7.5 0 0 
Hyperglycemia 15 0 0 
Hyponatremia 15 0 0 
Hypokalemia 12.5 0 0 
Hypomagnesemia 10 0 0 
Nausea 50 0 0 
Vomiting 17.5 0 0 
Diarrhea 10 2.5 0 
Constipation 5 0 0 
Mucositis 5 0 0 
Headache 2.5 0 0 
Sensory neuropathy 2.5 0 0 
Any Grade (%)Grade 3 (%)Grade 4 (%)
Hematologic    
Anemia 90 5 0 
Neutropenia 75 15 0 
Thrombocytopenia 7.5 0 0 
Nonhematologic    
Allergic reaction 12.5 0 0 
Hyperbilirubinemia 32.5 0 0 
ALT elevation 35 0 0 
AST elevation 27.5 0 0 
AKP elevation 30 0 0 
GGT elevation 32.5 2.5 0 
Hypoalbuminemia 85 0 0 
Hyperamylasemia 7.5 0 0 
Hyperglycemia 15 0 0 
Hyponatremia 15 0 0 
Hypokalemia 12.5 0 0 
Hypomagnesemia 10 0 0 
Nausea 50 0 0 
Vomiting 17.5 0 0 
Diarrhea 10 2.5 0 
Constipation 5 0 0 
Mucositis 5 0 0 
Headache 2.5 0 0 
Sensory neuropathy 2.5 0 0 

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

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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.

Topics:
asparaginase, extranodal disease, lymphoma, natural killer t-cells, nose, phase 2 clinical trials, chemotherapy regimen, adverse event, anemia, hypersensitivity

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2012 by The American Society of Hematology
2012
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