Forecasting optimal treatments in relapsed/refractory mature T‐ and NK ‐cell lymphomas: A global PETAL Consortium study

作者：Mark N Sorial, Jessy Xinyi Han, Min Jung Koh, Leora Boussi, Sijia Li, Rui Duan, Junwei Lu, Matthew Lei, Caroline T. MacVicar, Jessica Freydman, Jack Malespini, Kenechukwu Aniagboso, Sean M. McCabe, Luke Peng, Shambhavi Singh, Makoto Iwasaki, Ijeoma Julie Eche, Judith Gabler, María José Fernández, Aditya Garg, A. DiSciullo, Kusha Chopra, Josie Ford, Alexandra W Lenart, Emmanuel Nwodo, Jeffrey A. Barnes, Min Ji Koh, Eliana Miranda, Carlos Chiattone, Robert Stuver, Mwanasha H. Merrill, Eric D. Jacobsen, Martina Manni, Monica Civallero, Tetiana Skrypets, Athina Lymboussaki, Massimo Federico, Yu Ri Kim, Jin Seok Kim, Y. Choi, Thomas Eipe, Tanuja Shet, Sridhar Epari, Alok Shetty, Saswata Saha, Hasmukh Jain, Manju Sengar, Carrie van der Weyden, H. Miles Prince, Ramzi Hamouche, Tinatin Murdashvili, Francine M. Foss, Marianna Gentilini, Beatrice Casadei, Pier Luigi Zinzani, Takeshi Okatani, Noriaki Yoshida, Sang Eun Yoon, W. S. Kim, Girisha Panchoo, Zainab Mohamed, Estelle Verburgh, Jackielyn Cuenca Alturas, Mubarak Al‐Μansour, María Elena Cabrera, Amy Ku, Govind Bhagat, Helen Ma, Ahmed Sawas, K. Kariya, Forum Bhanushali, Arushi Meharwal, Dhruv Mistry, Maria Kosovsky, Mesrob Yeterian, Owen A. O’Connor, Enrica Marchi, Changyu Shen, Devavrat Shah, Salvia Jain · 发表于：British Journal of Haematology · 年份：2025 · DOI：10.1111/bjh.20063 · 被引用次数：4 · 研究领域：Lymphoma Diagnosis and Treatment、Genetic factors in colorectal cancer、Chronic Lymphocytic Leukemia Research

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...