First-Line Sintilimab With Pegaspargase, Gemcitabine, and Oxaliplatin for Patients With Advanced Extranodal Natural Killer/T-Cell Lymphoma

The combination of sintilimab, a programmed cell death protein 1 (PD-1) inhibitor, with pegaspargase, gemcitabine, and oxaliplatin (P-GEMOX) demonstrated efficacy and safety as a frontline regimen among patients with advanced extranodal natural killer/T-cell lymphoma, according to results from a phase 2 trial.

This multicenter, single-arm trial was conducted at 3 medical centers in China, and included 34 patients aged 18 to 75 years with treatment-naive pathologically confirmed advanced extranodal natural killer/T cell lymphoma and an with Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2. Investigators noted the primary end point was the complete response rate (CRR) in the intention-to-treat (ITT) population. Secondary end points included overall response rate (ORR), progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS).

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 3 weeks for 6 cycles, which was followed by intravenous sintilimab (200 mg) every 3 weeks for up to 2 years or until disease progression or unacceptable toxicities. The primary end point was the CRR in the ITT population.

Results from this study demonstrated a complete response rate of 85% (29 of 34 patients, 95% confidence interval [CI], 70 to 94), with 5 patients (15%; 95% CI, 7 to 30) attaining a partial response, with an ORR of 100% (34 of 34 patients). Additionally, the 24-month PFS measured at 64% (95% CI, 48 to 86), the 24-month DFS was 72% (54 to 95), and the 36-month OS was 76% (52 to 100).

Study authors noted the most common grade 3 or 4 treatment-related adverse events were neutropenia (17 [50%] of 34 patients), anemia (10 [29%] patients), and hypertriglyceridemia (10 [29%] patients). Hypothyroidism was the most frequent immune-related adverse event (18 [53%]), including grade 3 hypothyroidism in 1 (3%) patient that caused treatment to be discontinued. No severe adverse events occurred. There were 3 recorded deaths: 1 due to hemophagocytic syndrome, 1 due to disease progression, and 1 due to unknown cause, which were not considered to be treatment related.

“Combination of sintilimab with P-GEMOX seems to be an active and safe first-line regimen for patients with advanced [extranodal natural killer/T cell lymphoma],” concluded Xiao-Peng Tian, MD, Sun Yat-sen University Cancer Center, Guangzhou, China and colleagues.

Source:

Peng Tian X, Cai J, Xia Y, et al. First-line sintilimab with pegaspargase, gemcitabine, and oxaliplatin in advanced extranodal natural killer/T cell lymphoma (SPIRIT): A multicentre, single-arm, phase 2 trial. The Lancet Hem. 11,5: 336-344. doi: 10.1016/S2352-3026(24)00066-8