Forecasting optimal treatments in relapsed/refractory mature T- and NK-cell lymphomas: A global PETAL Consortium study
- Author(s)
- Sorial, MN; Han, JX; Koh, MJ; Boussi, L; Li, S; Duan, R; Lu, J; Lei, MM; MacVicar, CT; Freydman, J; Malespini, J; Aniagboso, KN; McCabe, SM; Peng, L; Singh, S; Iwasaki, M; Eche-Ugwu, IJ; Gabler, J; Fernandez Turizo, MJ; Garg, A; Disciullo, A; Chopra, K; Ford, J; Lenart, A; Nwodo, E; Barnes, J; Koh, MJ; Miranda, E; Chiattone, C; Stuver, R; Merrill, M; Jacobsen, E; Manni, M; Civallero, M; Skrypets, T; Lymboussaki, A; Federico, M; Kim, Y; Kim, JS; Cho, JY; Eipe, T; Shet, T; Epari, S; Shetty, A; Saha, S; Jain, H; Sengar, M; van der Weyden, C; Prince, HM; Hamouche, R; Murdashvili, T; Foss, F; Gentilini, M; Casadei, B; Zinzani, PL; Okatani, T; Yoshida, N; Yoon, SE; Kim, WS; Panchoo, G; Mohamed, Z; Verburgh, E; Alturas, JC; Al-Mansour, M; Cabrera, ME; Ku, A; Bhagat, G; Ma, H; Sawas, A; Kariya, KM; Bhanushali, F; Meharwal, A; Mistry, D; Kosovsky, M; Yeterian, M; O'Connor, OA; Marchi, E; Shen, C; Shah, D; Jain, S;
- Journal Title
- British Journal of Haematology
- Publication Type
- Research article
- Abstract
- 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.
- Publisher
- Wiley
- Keywords
- cytotoxic chemotherapy; epigenetic modifiers; machine learning; mature T‐cell and NK‐cell lymphomas; molecular therapeutics
- Department(s)
- Haematology
- Publisher's Version
- https://doi.org/10.1111/bjh.20063
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-07-08 04:31:34
Last Modified: 2025-07-08 04:32:02