The purpose of the SPIRIT trial is to determine the safety and efficacy of sintilimab with pegaspargase, gemcitabine and oxaliplatin (P-GemOx) for newly diagnosed advanced extranodal natural killer/T-cell lymphoma (ENKTL), nasal type.1
Programmed cell death protein 1 (PD-1) inhibitor sintilimab is effective in relapsed/refractory ENKTL, nasal type. The safety and activity of sintilimab plus P-GemOx in the first-line setting for advanced ENKTL was assessed in the SPIRIT trial.2
Methods
The multicentre, single-arm, phase II SPIRIT trial was done at three medical centres in China. Patients aged 18–75 years with treatment-naive pathologically confirmed advanced ENKTL and with an Eastern Cooperative Oncology Group performance status score of 0–2 were eligible. Patients received intravenous sintilimab (200 mg on day 1), intramuscular pegaspargase (2000 U/m2 on day 1), intravenous gemcitabine (1 g/m2 on days 1 and 8), and intravenous oxaliplatin (130 mg/m2 on day 1) every three weeks for six cycles, followed by intravenous sintilimab (200 mg) every three weeks for up to two years or until disease progression or unacceptable toxicities. The primary endpoint was complete response (CR) in the intention-to-treat population. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS).
Findings
Between November 29, 2019, and September 7, 2022, 34 eligible patients were enrolled (median age 39 years [IQR 32–55]; 25 [74%] of which 34 patients were male; nine [26%] were female; and all were of Asian ethnicity). At the data cut-off (July 20, 2023), the median follow-up was 21 months (IQR 13–32). The CR rate was 85% (29 of 34 patients, 95% CI 70–94). Five patients (15%; 95% CI 7–30) attained partial response and the ORR was 100%. Twenty-four-month PFS was 64% (95% CI 48–86), 24-month DFS was 72% (54–95), and 36-month OS was 76% (52–100). The most common grade 3 or 4 treatment-related adverse events were neutropenia (17 [50%] of 34 patients), anaemia (10 [29%] patients), and hypertriglyceridemia (10 [29%] patients). Hypothyroidism was the most frequent immune-related adverse event (18 [53%]), including grade 3 hypothyroidism in one patient that caused treatment termination. No severe adverse events occurred. There were three deaths: one due to haemophagocytic syndrome, one due to disease progression, and one due to unknown cause, which were not considered treatment related.
Conclusion
The combination of sintilimab + P-GemOx appears to be an effective and safe first-line treatment regimen for patients with advanced ENKTL, nasal type.2
REFERENCES
1. ClinicalTrials.gov ID NCT04127227. Sintilimab With P-GemOx (Pegaspargase, Gemcitabine and Oxaliplatin) Regimen for Newly Diagnosed Advanced Extranodal Natural Killer/T-cell Lymphoma, Nasal Type (ENKTL): a Single Arm, Open, Multicenter, Phase II Study. Accessed on 20 June 2024.
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