Purpose

Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive lymphoma with poor prognosis. The response rate to L-asperagenase(L-ASP) based multi-agent regimens is highly effective. Several clinical trials demonstraed good response and less toxicity for pegaspargase (PEG-ASP) in comparison to L-ASP. This is the first prospective study to evaluate the efficacy and safety of PEG-ASP combined with gemcitabine and oxaliplatin (PEG-ASP + Gemox) for patients with treatment-naïve and refractory or relapsed ENKTL.

Patients and methods

61 eligible patients treated by PEG-ASP + Gemox from March 2010 to March 2013 were analyzed. 36 newly -diagnosed patients and 25 refracrory/replased patients were enrolled, we also conducted extra matched-pair analysis between 20 stage IE/IIE cases selected from 36 newly -diagnosed patients in PEG-ASP + Gemox group and 18 stage IE/IIE patients in L-ASP + Gemox regimen group(unpublished data, Table 1,2). PEG-ASP + Gemox dosages were as follows: Gemcitabine 1000 mg/m2; day 1,8; oxaliplatin 130 mg/m2 day 1, PEG-ASP 2500 U/m2 im day1. The regimen was repeated every 3 weeks for a maximum of 6 cycles including 3 cycles induction chemotherapy for stage IE/IIE patients followed by involved-field radiotherapy. Furthermore autologous haematopoietic stem cell transplantation(AHSCT) was recommended to refractory/relapsed patients after achieved good response.

Table 1.

Efficacy for newly diagnosed stage IE/IIE ENKTL patients

  Whole group L-ASP+Gemox PEG-ASP+Gemox 
  Chemo % (n) Radiochemo % (n) Chemo % (n) Radiochemo % (n) Chemo % (n) Radiochemo % (n) 
RR 86.8(33/38) 92.1 (35/38) 88.9 (16/18) 100 (18/18) 85.0 (17/20) 95.0 (19/20) 
CR 71.1(27/38) 84.2 (32/38) 72.2 (13/18) 77.7 (14/18) 80.0(16/20) 90.0(18/20) 
PR 15.8 (6/38) 7.9(3/38) 16.7 (3/18) 22.3 (4/18) 5.0(1/20) 5.0 (1/20) 
SD 13.2 (5/38) 7.9 (3/38) 11.1 (2/18) 0 15.0 (3/20) 5.0(1/20) 
2-year OS 94.7% 83.3% 100% 
2-year PFS 88.5% 82.5% 87.1% 
  Whole group L-ASP+Gemox PEG-ASP+Gemox 
  Chemo % (n) Radiochemo % (n) Chemo % (n) Radiochemo % (n) Chemo % (n) Radiochemo % (n) 
RR 86.8(33/38) 92.1 (35/38) 88.9 (16/18) 100 (18/18) 85.0 (17/20) 95.0 (19/20) 
CR 71.1(27/38) 84.2 (32/38) 72.2 (13/18) 77.7 (14/18) 80.0(16/20) 90.0(18/20) 
PR 15.8 (6/38) 7.9(3/38) 16.7 (3/18) 22.3 (4/18) 5.0(1/20) 5.0 (1/20) 
SD 13.2 (5/38) 7.9 (3/38) 11.1 (2/18) 0 15.0 (3/20) 5.0(1/20) 
2-year OS 94.7% 83.3% 100% 
2-year PFS 88.5% 82.5% 87.1% 

Chemo meanschemotherapy; radiochemo means radiochemotherapy

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Table 2.

Toxicities of of newly diagnosed stage IE/IIE ENKTL patients

  Any grade Grade 3/4  
L-ASP+Gemox (56 cycles) % (n) PEG-ASP+Gemox (64 cycles) % (n) L-ASP+Gemox (56 cycles) (%) % (n) PEG-ASP+Gemox (64 cycles) % (n) P 
Neutropenia 71.4(40) 68.8 (44) 17.9 (10) 17.2 (11) 0.843 
Thrombocytopenia 57.1 (32) 46.9 (30) 14.3 (8) 14.1 (9) 0.278 
Anemia 60.7 (34) 45.3 (29) 8.9 (5) 3.1 (2) 0.102 
AST/ALT elevated 58.9 (33) 39.0 (25) 3.6 (2) 4.7 (3) 0.554 
Hypoproteinemia 33.9(19) 20.3 (13) 5.4 (3) 0 0.102 
Fbg decrease 53.6(30) 35.9 (23) 7.1 (4) 3.1 (2) 0.066 
Nausea* 46.4 (26) 26.6 (17) 0 0 0.035 
Anorexia 57.1 (32) 39.0 (25) 0 0 0.067 
Vomiting 35.7 (20) 21.5 (14) 0 0 0.107 
Allergic reactions* 17.9 (10) 1.6 (1) 0 0 0.003 
Intestinal hemorrhage 3.6(2) 0 1.6(1) 0 0.216 
intracranial hemorrhage 0 3.2 (2) 0 0 0.498 
pancreatitis 3.6 (2) 1.6 (1) 0 0 0.598 
 
  Any grade Grade 3/4  
L-ASP+Gemox (56 cycles) % (n) PEG-ASP+Gemox (64 cycles) % (n) L-ASP+Gemox (56 cycles) (%) % (n) PEG-ASP+Gemox (64 cycles) % (n) P 
Neutropenia 71.4(40) 68.8 (44) 17.9 (10) 17.2 (11) 0.843 
Thrombocytopenia 57.1 (32) 46.9 (30) 14.3 (8) 14.1 (9) 0.278 
Anemia 60.7 (34) 45.3 (29) 8.9 (5) 3.1 (2) 0.102 
AST/ALT elevated 58.9 (33) 39.0 (25) 3.6 (2) 4.7 (3) 0.554 
Hypoproteinemia 33.9(19) 20.3 (13) 5.4 (3) 0 0.102 
Fbg decrease 53.6(30) 35.9 (23) 7.1 (4) 3.1 (2) 0.066 
Nausea* 46.4 (26) 26.6 (17) 0 0 0.035 
Anorexia 57.1 (32) 39.0 (25) 0 0 0.067 
Vomiting 35.7 (20) 21.5 (14) 0 0 0.107 
Allergic reactions* 17.9 (10) 1.6 (1) 0 0 0.003 
Intestinal hemorrhage 3.6(2) 0 1.6(1) 0 0.216 
intracranial hemorrhage 0 3.2 (2) 0 0 0.498 
pancreatitis 3.6 (2) 1.6 (1) 0 0 0.598 
 
*

P<0.05

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Results

55 patients were evaluable for response after a median 4 (1¨C6 ) cycles. The overall response(OR) rate was 90.9% (50/55), with a complete remission (CR) rate of 60.0% (33/55). After a median follow-up of 16.2 (4.0-39.5)months, the 1-, 2-year OS rates were 88.2%, 83.2%, and the 1-, 2- year PFS rates were all 85.2%. The median follow-up time was 19.6 (4.0-39.5)months for treatmen-naive patients. their OR, CR, partial remission(PR) rates were 94.0% (31/33), 66.7% (22/33), 27.3% (9/33), respectively. Both 1-, 2-year OS rates were 94.0%, 1-, 2-year PFS rates were all 93.9%. The median follow-up time was 18.7(4.5-36.2) months for refractory/replased patients. The OR and CR rates were 86.4% (19/22), 50.0% (11/22). The 1-, 2-year OS rates were 80.4% ,70.4%, the 1-, 2-year PFS rates were all 72.7%. Patients who achieved CR had undergone a median of two cycles (2¨C6). All patients received 187 cycles of chemotherapy, the incidence of rates of grade 1 and 2 adverse events were as follows: neutropenia, 69.6%; vomit 39.5%, transaminase elevation, 37.9%. Grade 3 and 4 adverse reactions were rare.

Conclusion

Our clinical trisl have demonstrated high efficacy and quick achievement of CR for the first time for PEG-ASP+Gemox regimen in the management of treatment-naïve and refractory/relapsed ENKTL patients. It also provided good chance of AHSCT as consolidation for chemosensitive patients. Meanwhile, PEG-ASP+Gemox regimen was conveniant and less toxic. Further investigation for PEG-ASP + Gemox regimen is warranted.

Disclosures:

No relevant conflicts of interest to declare.

Figure 1
Figure 1. Overall survival of chemonaive compared with refractory/relapsed patients.
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Overall survival of chemonaive compared with refractory/relapsed patients.

Figure 1
Figure 1. Overall survival of chemonaive compared with refractory/relapsed patients.
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Overall survival of chemonaive compared with refractory/relapsed patients.

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Topics:
extranodal disease, gemcitabine, lymphoma, natural killer t-cells, oxaliplatin, pegaspargase, chemotherapy regimen, lymphoma, extranodal nk-t-cell, asparaginase, follow-up

Author notes

*

Asterisk with author names denotes non-ASH members.

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© 2013 by The American Society of Hematology
2013
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