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

  


Authors: Sorial, M. N.; Han, J. X.; Koh, M. J.; Boussi, L.; Li, S.; Duan, R.; Lu, J.; Lei, M. M.; MacVicar, C. T.; Freydman, J.; Malespini, J.; Aniagboso, K. N.; McCabe, S. M.; Peng, L.; Singh, S.; Iwasaki, M.; Eche-Ugwu, I. J.; Gabler, J.; Fernandez Turizo, M. J.; Garg, A.; Disciullo, A.; Chopra, K.; Ford, J.; Lenart, A.; Nwodo, E.; Barnes, J.; Koh, M. J.; Miranda, E.; Chiattone, C.; Stuver, R.; Merrill, M.; Jacobsen, E.; Manni, M.; Civallero, M.; Skrypets, T.; Lymboussaki, A.; Federico, M.; Kim, Y.; Kim, J. S.; Cho, J. Y.; Eipe, T.; Shet, T.; Epari, S.; Shetty, A.; Saha, S.; Jain, H.; Sengar, M.; Van Der Weyden, C.; Prince, H. M.; Hamouche, R.; Muradashvili, T.; Foss, F.; Gentilini, M.; Casadei, B.; Zinzani, P. L.; Okatani, T.; Yoshida, N.; Yoon, S. E.; Kim, W. S.; Panchoo, G.; Mohamed, Z.; Verburgh, E.; Alturas, J. C.; Al-Mansour, M.; Cabrera, M. E.; Ku, A.; Bhagat, G.; Ma, H.; Sawas, A.; Kariya, K. M.; Bhanushali, F.; Meharwal, A.; Mistry, D.; Kosovsky, M.; Yeterian, M.; O'Connor, O. A.; Marchi, E.; Shen, C.; Shah, D.; Jain, S.
Article Title: Forecasting optimal treatments in relapsed/refractory mature T- and NK-cell lymphomas: A global PETAL Consortium study
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. © 2025 British Society for Haematology and John Wiley & Sons Ltd.
Keywords: adult; controlled study; aged; middle aged; retrospective studies; overall survival; lenalidomide; clinical trial; mortality; methotrexate; antineoplastic agent; t lymphocyte; antineoplastic combined chemotherapy protocols; cohort analysis; recurrence; retrospective study; peripheral t cell lymphoma; t cell lymphoma; lymphoma, t-cell; multicenter study; tipifarnib; forecasting; recurrent disease; drug therapy; therapy; pralatrexate; retinoid; nk t cell lymphoma; calcineurin; machine learning; cytotoxic chemotherapy; angioimmunoblastic t cell lymphoma; humans; human; male; female; article; extranodal natural killer/t-cell lymphoma; microbial consortium; breast cancer recurrence; lymphoma, extranodal nk-t-cell; sulanemadlin; epigenetic modifiers; mature t-cell and nk-cell lymphomas; molecular therapeutics; petal
Journal Title: British Journal of Haematology
Volume: 206
Issue: 6
ISSN: 0007-1048
Publisher: John Wiley & Sons  
Date Published: 2025-01-01
Start Page: 1664
End Page: 1677
Language: English
DOI: 10.1111/bjh.20063
PUBMED: 40310502
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-105004279153&doi=10.1111%2fbjh.20063&partnerID=40&md5=e4c32270582ba2e0dd835b35df18185e
Notes: Article -- Source: Scopus
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
BMJ Impact Analytics
Related MSK Work