结外自然杀伤/T 细胞淋巴瘤中对天冬酰胺酶和 PD-1 阻断的双重耐药：多中心队列的不良结局

Asparaginase-based regimens and anti-PD-1 therapies have significantly improved survival in patients with extranodal natural killer/T-cell lymphoma (ENKTL) and are now increasingly incorporated into earlier treatment lines.

However, clinical outcomes for patients with dual resistance to asparaginase and PD-1 inhibitors remain poorly defined.

We conducted a multicenter retrospective study of 61 patients with dual resistance from a cohort of 900 ENKTL patients across 12 academic centers in China. Among 61 patients, median overall survival from initial diagnosis (OS-1) was 21. 9 months (95% CI: 14. 7-43. 1). After the onset of dual resistance, the median post-resistance survival (OS-2) was 4. 9 months (95% CI: 2. 8-9. 9). Rechallenge with asparaginase-based regimens or anti-PD-1 agents resulted in only limited benefit, yielding median progression-free survival (PFS) of 3. 2 months (95% CI: 1. 4-5. 0) and 2.

7 months (95% CI: 2. 1-3. 3), respectively. Chidamide-containing regimens were associated with a significantly longer OS-2 compared to regimens without chidamide (HR, 0. 46; 95% CI: 0. 24-0. 88; P = 0. 019).

Other novel agents, including inhibitors of XPO1, PI3K, and JAK1, along with brentuximab vedotin, did not demonstrate a significant survival benefit in patients with dual-resistant ENKTL. This is the first comprehensive analysis of dual-resistant ENKTL, revealing poor prognosis and suggesting a potential signal of benefit associated with chidamide-containing regimens.