预测复发/难治性成熟 T 细胞和 NK 细胞淋巴瘤的最佳治疗：一项全球 PETAL 联盟研究

There is no standard of care in relapsed/refractory T-cell/natural killer-cell lymphomas. Patients often cycle through cytotoxic chemotherapy (CC), epigenetic modifiers (EM) or small molecule inhibitors (SMI) empirically. Ideal therapy at each line remains unknown.

We conducted a retrospective, multiple intervention, 'target-trial' using the PETAL global cohort. Patients received front-line CC, then second and third line (2L and 3L) with either CC again, EM or SMI (12 possible treatment scenarios).

Overall survival (OS; 2L or 3L to death) was compared across treatment sequences using Cox, reinforcement learning and synthetic intervention methods adjusting for age, histology, primary refractory disease, prognostic index for T-cell lymphoma (PIT) score, response to 2L, and receipt of 2L transplant consolidation. Five hundred and forty received 2L (EM = 101, SMI = 45, CC = 394), and 290 received 3L (EM = 65, SMI = 44, CC = 181). 2L SMI then 3L EM improved OS (adjusted hazard ratio [aHR]: 0. 29, 95% confidence interval [CI]: 0. 11-0. 74; p = 0.

010) versus 2L-3L CC-CC, and consistently across most other sequential strategies. In 2L stability analyses, benefit was notable with 2L SMI in angioimmunoblastic T-cell lymphoma (vs. CC: aHR: 0. 23, 95% CI: 0. 10-0. 4; p < 0. 001); vs. EM: aHR: 0. 32, 95% CI: 0. 12-0. 82; p = 0.

020), and both SMI and EM in PIT-stratified high-risk groups (SMI: aHR: 0. 40, 95% CI: 0. 21-0. 76; p = 0. 005; EM: aHR: 0. 60, 95% CI: 0. 39-0. 92; p = 0. 020) versus 2L CC. Results were consistent across all other independent stability and causal inference analyses providing a treatment selection framework.