Abstract

Background

The prognosis of NTCL patients presenting in stage III/IV is extremely poor and there is no standard chemotherapy. Although L-asparaginase (L-asp) is known to be effective for NTCL, its significance has not been well demonstrated in a relatively homogenous subset. In addition, there were few studies to evaluate treatment outcomes and prognostic factors in stage III/IV NTCL. This study was undertaken to evaluate the efficacy of L-asparaginase-based combination chemotherapy (IMEP plus L-asp) and prognostic factors in stage III/IV NTCL.

Methods

A total of 70 patients with newly diagnosed NTCL at stage III/IV were enrolled from 3 Korean centers between Jan 2000 and Feb 2013. All patients received IMEP plus L-asp (N=22) regimens or combination chemotherapy without L-asp (N=48) as a first-line treatment. Recurrent cases were excluded. Clinical prognostic factors, treatment outcomes, and prognostic scores were compared between the groups. Independent prognostic factors for survivals were identified using multivariate analyses.

Results

The median age was 48.5 years (range, 18-73 years) with a male-to-female ratio of 2.2:1. After a median follow-up period of 12.8 months (range, 1.1-186.6 months), median progression-free survival (PFS) and overall survival (OS) were 5.6 months and 12.3 months, respectively. Clinical factors and treatment outcomes were compared between IMEP plus L-asp and chemotherapy without L-asp groups (Table 1). Higher response rate (RR) and complete response (CR) rates were observed in patients treated with IMEP plus L-asp compared with those treated with chemotherapy without L-asp (RR 90.0% vs. 34.8%, P< 0.0001; and CR rates 65.0% vs. 21.7%, P = 0.001). In addition, PFS and OS were significantly higher for IMEP plus L-asp group compared with chemotherapy without L-asp group (Table 1). Use of chemotherapy without L-asp (hazards ratio [HR]=2.29, 95% confidence interval [CI] 1.22-4.29; P = 0.010) and poor performance status (HR=2.10, 95% CI 1.23-3.59; P = 0.007) were independent predictors for reduced PFS. Independent factors adversely affecting OS were poor performance status (HR=1.99, 95% CI 1.08-3.65; P = 0.027), 2 or more extranodal sites (HR=2.91, 95% CI 1.25-6.77; P = 0.013), and chemotherapy without L-asp (HR=3.51, 95% CI 1.53-8.06; P= 0.003).

Table1.

Patients’ characteristics and treatment outcomes between the groups

     
Clinical factors and Outcomes Chemotherapy without L-asp
N= 48 (%) 
IMEP plus L-asp
N= 22 (%) 
P 
Age ≤ 60 years
> 60 years 
35 (72.9)
13 (27.1) 
20 (90.9)
2 (9.1) 
0.121 
B symptoms No
Yes 
12 (25.0)
36 (75.0) 
10 (45.5)
12 (54.5) 
0.087 
LDH Normal
Elevated 
6 (12.5)
42 (87.5) 
6 (27.3)
16 (72.7) 
0.128 
No. extranodal sites 0-1
≥ 2 
12 (25.0)
36 (75.0) 
4 (18.2)
18 (81.8) 
0.760 
International Prognostic Index 0-2
3-4 
8 (16.7)
40 (83.3) 
8 (36.4)
14 (63.6) 
0.068 
Response rate  16/46
(34.8%) 
18/20
(90.0%) 
< 0.0001 
CR rate  10/46
(21.7%) 
13/20
(65.0%) 
0.001 
Remission duration Median (months) 5.8 10.7 0.128 
PFS Median (months)
1-year PFS (%) 
3.2
16.7 
10.1
43.3 
0.002 
OS Median (months)
1-year OS (%) 
5.7
37.5 
Not reached
83.9 
0.001 
     
Clinical factors and Outcomes Chemotherapy without L-asp
N= 48 (%) 
IMEP plus L-asp
N= 22 (%) 
P 
Age ≤ 60 years
> 60 years 
35 (72.9)
13 (27.1) 
20 (90.9)
2 (9.1) 
0.121 
B symptoms No
Yes 
12 (25.0)
36 (75.0) 
10 (45.5)
12 (54.5) 
0.087 
LDH Normal
Elevated 
6 (12.5)
42 (87.5) 
6 (27.3)
16 (72.7) 
0.128 
No. extranodal sites 0-1
≥ 2 
12 (25.0)
36 (75.0) 
4 (18.2)
18 (81.8) 
0.760 
International Prognostic Index 0-2
3-4 
8 (16.7)
40 (83.3) 
8 (36.4)
14 (63.6) 
0.068 
Response rate  16/46
(34.8%) 
18/20
(90.0%) 
< 0.0001 
CR rate  10/46
(21.7%) 
13/20
(65.0%) 
0.001 
Remission duration Median (months) 5.8 10.7 0.128 
PFS Median (months)
1-year PFS (%) 
3.2
16.7 
10.1
43.3 
0.002 
OS Median (months)
1-year OS (%) 
5.7
37.5 
Not reached
83.9 
0.001 
Conclusions

L-asparaginase-based combination chemotherapy (IMEP plus L-asp) is active against stage III/IV NTCL and an independent predictor for improved survivals. L-asp containing regimen might be useful as a first-line treatment for stage III/IV NTCL.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.