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SAN FRANCISCO—Results of a single-center study suggest that a 3-drug regimen may be a safe and effective treatment option for patients with newly diagnosed or relapsed/refractory extranodal natural killer/T-cell lymphoma (ENKTL).

The combination of pegaspargase, gemcitabine, and oxaliplatin (P-Gemox) elicited a high rate of response in this cohort of 60 Chinese patients.

P-Gemox also produced higher survival rates than those previously observed with the EPOCH regimen.

Grade 1/2 myelosuppression occurred in more than half of patients in this study, and nearly three-quarters of patients experienced grade 1/2 nausea. But grade 3/4 adverse events were minimal.

Hui-qiang Huang, MD, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China, presented these results at the 6th Annual T-cell Lymphoma Forum.

Dr Huang noted that advanced ENKTL is relatively resistant to anthracycline-based chemotherapy. And although the SMILE and AspaMetDex regimens are effective, they confer relatively severe toxicities and are inconvenient to administer.

“So chemotherapeutic combinations with high efficacy and low toxicities are urgently needed,” he said.

With this in mind, he and his colleagues assessed P-Gemox in 61 patients with ENKTL. Thirty-six patients were newly diagnosed, and 25 had relapsed/refractory disease. Roughly 69% of patients were male, and about 86% were older than 60 years of age.

Overall, 36.1% of patients had stage IE disease, 31.1% had stage IIE, 4.9% had stage IIIE, and 27.9% had stage IVE.

The relapsed/refractory patients had received a range of prior treatment regimens, including CHOP/L-ASP+CHOP, EPOCH, V-EPOCH, ICE, IMVP-16, and SMILE. And 13 patients had received radiotherapy.

For this study, all 61 patients received intravenous gemcitabine at 1000 mg/m2 on days 1 and 8, intravenous oxaliplatin at 130 mg/m2 on day 1, and intramuscular pegaspargase at 2500 U/m2 on day 1. This regimen was repeated every 3 weeks.

Patients with stage IE/IIE disease received 3 cycles followed by radiotherapy (50-56 Gy). Relapsed/refractory patients received 2 to 6 cycles, and those who responded well were recommended for autologous transplant.

Response and subsequent treatment

Sixty patients were evaluable for response. (One patient in the newly diagnosed group was not evaluable).

The overall response rate (ORR) was 90%, with 63.3% of patients achieving a complete response (CR), 26.7% achieving a partial response (PR), and 8.3% maintaining stable disease (SD).

Among newly diagnosed patients, the ORR was 94.3%. CRs occurred in 74.3% of patients, PRs in in 20%, and SD in 5.7%.

And among the relapsed/refractory patients, the ORR was 84%. CRs were seen in 48% of patients, PRs in 36%, and SD in 12%.

“For patients with early stage disease, we found P-Gemox can further improve the outcomes of radiotherapy,” Dr Huang noted.

The treatment also provided a good bridge to transplant. Eight patients underwent transplant after achieving CR. One of these patients died 9 months after the procedure, but the other 7 patients were still in CR at a median of 14.6 months (range, 4.8-19.7 months).

‘Encouraging’ survival

The median follow-up was 29.5 months. The researchers confirmed progressive disease in 18 of the 61 patients—7 in the newly diagnosed group and 11 in the relapsed/refractory group.

Nine patients died of disease progression—1 in the newly diagnosed group and 8 in the relapsed/refractory group.

The 2-year overall survival was 86%, and the 2-year progression-free survival was 75.6%. Both overall and progression-free survival were superior in the newly diagnosed patients (P=0.054 and P=0.004, respectively).

“For the relapsed/refractory cases, considering they had already received a lot of previous treatments, we thought this outcome with P-Gemox is still quite encouraging,” Dr Huang said.

When the researchers compared overall survival with P-Gemox to previous results observed with EPOCH in newly diagnosed ENKTL patients (Huang et al, Leuk & Lymph 2011), they found P-Gemox was superior.

‘Tolerable’ toxicity

Toxicity with P-Gemox was tolerable and manageable, according to Dr Huang. The main adverse events were nausea and myelosuppression. But the rate of grade 3/4 events was low, and there were no treatment-related deaths.

Specifically, the grade 1/2 adverse events included nausea (73.8%), neutropenia (58%), thrombocytopenia (52.4%), hypoprotinemia (52.4%), anemia (52.4%), vomiting (49.2%), prolonged APTT (44.2%), elevated transaminase (34.1%), elevated bilirubin (27.9%), mucositis (24.5%), decreased fibrinogen (23%), elevated BUN (4.9%), intracranial bleeding (1.6%), stomach bleeding (1.6%), pancreatitis (1.6%), and herpes (1.6%).

Grade 3/4 adverse events included neutropenia (19.7%), thrombocytopenia (16.4%), hypoprotinemia (1.6%), anemia (1.6%), vomiting (3.2%), elevated transaminase (1.6%), and decreased fibrinogen (1.6%).

“We found that P-Gemox is an effective, safe, and convenient regimen in Chinese patients with ENKTL, both treatment-naïve and relapsed/refractory,” Dr Huang concluded. “These results provide a basis for subsequent studies.”

Dr Huang and his colleagues also presented the results of this research at the ASH Annual Meeting in December as abstract 642. (Information presented at the T-cell Lymphoma Forum differs from that in the ASH abstract). ht-logo-end

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