Clinical Outcome of P-Gemox ( Pegaspargase, Gemcitabine, Oxaliplatin ) for the Patients with Newly Diagnosed Stage III/IV or Relapsed/Refractory Extranodal Natural Killer/T Cell Lymphoma

Purpose

Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive form of non-Hodgkin¡¯s lymphoma. The prognosis for patients with advanced stages or relapsed/ refractory ENKTL is extremely poor. Optimal combined chemotherapy remain to be defined. Therefore, the purpose of this study is to evaluate efficacy and safety of P-GEMOX (Pegaspargase, Gemcitabine and Oxaliplatin ) in patients with newly diagnosed stage III/IV or relapsed/refractory ENKTL.

Patients and methods

We retrospectively analyzed the effectiveness and toxicity of P-GEMOX in 60 patients with newly diagnosed stage III/IV and relapsed/refractory ENKTL between February 2008 and August 2014. The P-GEMOX dosage was as follows:  Gemcitabine 1000 mg/m²  iv  d1,d8;  Oxaliplatin 100 mg/m²; d 1,  Pegaspargase 2000 U/m² im, two different sites. The regimen was repeated every three weeks for a maximum six cycles. Patients underwent autologous hematopoietic stem cell transplantation (ASCT) as consolidation if they achieved CR.

Results

57 patients were available for evaluation of response. The objective response, complete remission(CR), of whole cohort were 73.7% (42/57), 36.8% (21/57),  respectively. It can be easily administered in out-patients clinic. The median follow-up was 29.1 (range, 2.4¨C54.2 months). Median OS and PFS was 23.0 months (95% confidence interval [CI], 16.441-29.559) and 12.8 months(95% confidence interval [CI], 8.109-17.491), respectively. The 4-year OS and PFS rate was 43.0¡À7.3% and 36.5¡À6.9%, respectively (Figure1). There was no difference between newly diagnosed stage III/IV and relapsed/refractory in OS and PFS. The long term survival CR responders were superior to patients with other response, and there was significant difference between the three group(Figure 2, P<0.001). Eleven patients accepted ASCT after achievement of CR, 3-year OS rate were better than other patients( 68.2% vs. 36.6%£¬P=0.08, Figure 3). Toxicities (>50%) : neutropenia (85.0%), thrombocytopenia (72.0%), hypoproteinemia (86.7%), and anorexia (63.3%). In addition, hypofibrinogenemia  was 46.7%. The most common grade III/IV toxicities (>10%) were granulocytosis (31.6%), thrombocytopenia (26.67%) and hypoproteinemia (13.3%)(Table 1). Intracranial bleeding occurred in one patient during the first cycle with discontinuation of pegaspargase  in the consecutive cycles. No treatment related death confirmed.

Conclusion

The P-GEMOX regimen is a safe and effective  combination for newly diagnosed  advanced  and relapsed/refractory ENKTL. Promising long term outcome can be expected by addition of ASCT  consolidation after response to induction chemotherapy. In comparison to other combined regimen in literatures, P-GEMOX is effective with less toxic, simplified and high cost-effective .  Further clinical trials urgently needed.

Figure.1.   4-year OS and PFS of whole patients

Figure.2.   Survival of whole patients,  based on response

  

Figure.3.  OS: patients with ASCT vs. Non-ASCT

Table 1. Toxicities of whole cohort

	All cases (%)	Grade 1/2 (%)	Grade 3/4 (%)
Toxicities
Neutropenia	51(85.0)	32(53.3)	19(31.6)
Thrombocytopenia	22(36.7)	15(25.0)	7(11.7)
Anemia	43(71.6)	18(66.7)	3(5.0)
lymphocytoponia	14(23.3)	12(20.0)	2(3.3)
AST/ALT elevated	26(43.3)	22(36.7)	4(6.7)
Hypoproteinemia	53(88.3)	48(84.9)	8(13.3)
Fbg decrease	41(68.3)	39(65.0)	2(3.3)
APTT prolong	16(26.7)	16(26.7)	0
Hyperglycemia	7(11.6)	7(11.6)	0
Total bilirubin elevated	9(15.0)	9(15.0)	0
Nausea	21(35.0)	21(35.0)	0
Anorexia	32 (53.3)	32 (53.3)	0
Vomiting	19(31.6)	19(31.6)	0
Allergic reactions	1(1.7)	1(1.7)	0
herpes zoster	3(5.0)	3(5.0)	0