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

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.

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Publication Details

Journal
British Journal of Haematology
Published
2025-05-01
DOI
https://doi.org/10.1111/bjh.20063
Citations
2
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
2.94

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article

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

Owen A. O’Connor, Mark N Sorial, Noriaki Yoshida, Junwei Lu et al.
2 citations
British Journal of Haematology
Lymphoma Diagnosis and Treatment
2.94
article

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

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

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.

British Journal of HaematologyVol. 206(6)
Broad Institute (US), University of Modena and Reggio Emilia (IT), Northeastern University (US), Biogen (United States) (US), Beth Israel Deaconess Medical Center (US), Memorial Sloan Kettering Cancer Center (US), NewYork–Presbyterian Brooklyn Methodist Hospital (US), Harvard University (US), University of Cape Town (ZA), The University of Melbourne (AU), Universidade Estadual de Campinas (UNICAMP) (BR), Georgetown University (US), Yonsei University (KR), Homi Bhabha National Institute (IN), University of California, Irvine (US), Radiation Effects Research Foundation (JP), Columbia University Irving Medical Center (US), Tata Memorial Hospital (IN), Santa Casa Hospital (BR), Peter MacCallum Cancer Centre (AU), Samsung Medical Center (KR), Groote Schuur Hospital (ZA), King Abdulaziz Medical City (SA), Yale Cancer Center (US), Massachusetts General Hospital (US), Hospital del Salvador (CL), Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital (JP), Dana-Farber Cancer Institute (US), Istituto di Ematologia di Bologna (IT), Istituto Tumori Bari (IT), Gangnam Severance Hospital (KR), Istituti di Ricovero e Cura a Carattere Scientifico (IT), VA Long Beach Healthcare System (US), University of Virginia (US), Massachusetts Institute of Technology (US), University of Chile (CL), Sungkyunkwan University (KR), University of Bologna (IT)
Kyowa Hakko Kirin, Daiichi Sankyo Europe
Openalex Percentile: Top 10%
Lymphoma Diagnosis and Treatment
2.94
DOISourceOpenAlex
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