: We previously demonstrated that relapsed and refractory nodal-mature-T-cell-lymphomas (nMTCL) have distinct prognoses. Here, we assessed the overall survival (OS) impact of time-to-relapse (TTR) in multinational PETAL/LATAM cohorts with validation using observational and randomized independent cohorts. Patients with nMTCL with complete response to frontline treatment were assigned to TTR12 (<12m) or without TTR12 based on time-to-progression or time-to-next-therapy. OS was compared using modified landmark (m-LM) analysis. Sensitivity analyses included standard landmark (s-LM) and time-dependent Cox (td-Cox). Estimates were adjusted for age, histology, and Prognostic-Index-for-T-cell-lymphoma (PIT) score. Across 452 patients, 165 (36.5%) had TTR12, 181 (40%) relapsed ≥12m, and 106 (23.5%) remained relapse-free. TTR12 conferred worse OS using m-LM (HR 2.14; 95%CI: 1.58-2.90, p<0.001), s-LM (HR 1.92; 95%CI: 1.39-2.66, p<0.001), and td-Cox (HR 5.81; 95%CI: 2.94-11.46, p<0.001). Results were consistent in the independent validation cohorts with univariable and multivariable models. TTR12 consistently conferred worse OS irrespective of front-line hematopoietic stem-cell transplantation or PIT score, in peripheral-T-cell-lymphoma, not-otherwise-specified (m-LM: HR 2.32; 95%CI: 1.51-3.55, p<0.001; s-LM: HR 2.10; 95%CI: 1.33-3.31, p=0.001), anaplastic-large-cell-lymphoma (m-LM: HR 3.34; 95%CI: 1.18-9.50, p=0.023; s-LM: HR 2.96; 95%CI: 1.02-8.81, p=0.046), and angioimmunoblastic-T-cell/T-follicular-helper-cell-lymphoma (m-LM only: HR 1.92, 95%CI: 1.15-3.21; p=0.013). Second-line novel therapies improved OS (second-line start to death) versus chemotherapy in TTR12 (HR 0.60; 95%CI: 0.37-0.97, p=0.038) but not in patients without (HR 0.82; 95%CI: 0.51-1.32, p=0.407). TTR12 identified worse OS patients alongside, and compounding with, PIT score. TTR12 serves as a prognostic and potential OS surrogate marker, supporting stratification of new risk groups and need for their differential treatment.
Sorial, M.N., Malpica, L., Chiattone, C.S., Julia, E., Bachy, E., Barta, S.K., et al. (2025). Early time to relapse as a survival prognosticator in mature T-cell/NK-cell lymphomas: results from the PETAL Consortium. BLOOD, 1, 1-1 [10.1182/blood.2025030149].
Early time to relapse as a survival prognosticator in mature T-cell/NK-cell lymphomas: results from the PETAL Consortium
Zinzani, Pier Luigi;
2025
Abstract
: We previously demonstrated that relapsed and refractory nodal-mature-T-cell-lymphomas (nMTCL) have distinct prognoses. Here, we assessed the overall survival (OS) impact of time-to-relapse (TTR) in multinational PETAL/LATAM cohorts with validation using observational and randomized independent cohorts. Patients with nMTCL with complete response to frontline treatment were assigned to TTR12 (<12m) or without TTR12 based on time-to-progression or time-to-next-therapy. OS was compared using modified landmark (m-LM) analysis. Sensitivity analyses included standard landmark (s-LM) and time-dependent Cox (td-Cox). Estimates were adjusted for age, histology, and Prognostic-Index-for-T-cell-lymphoma (PIT) score. Across 452 patients, 165 (36.5%) had TTR12, 181 (40%) relapsed ≥12m, and 106 (23.5%) remained relapse-free. TTR12 conferred worse OS using m-LM (HR 2.14; 95%CI: 1.58-2.90, p<0.001), s-LM (HR 1.92; 95%CI: 1.39-2.66, p<0.001), and td-Cox (HR 5.81; 95%CI: 2.94-11.46, p<0.001). Results were consistent in the independent validation cohorts with univariable and multivariable models. TTR12 consistently conferred worse OS irrespective of front-line hematopoietic stem-cell transplantation or PIT score, in peripheral-T-cell-lymphoma, not-otherwise-specified (m-LM: HR 2.32; 95%CI: 1.51-3.55, p<0.001; s-LM: HR 2.10; 95%CI: 1.33-3.31, p=0.001), anaplastic-large-cell-lymphoma (m-LM: HR 3.34; 95%CI: 1.18-9.50, p=0.023; s-LM: HR 2.96; 95%CI: 1.02-8.81, p=0.046), and angioimmunoblastic-T-cell/T-follicular-helper-cell-lymphoma (m-LM only: HR 1.92, 95%CI: 1.15-3.21; p=0.013). Second-line novel therapies improved OS (second-line start to death) versus chemotherapy in TTR12 (HR 0.60; 95%CI: 0.37-0.97, p=0.038) but not in patients without (HR 0.82; 95%CI: 0.51-1.32, p=0.407). TTR12 identified worse OS patients alongside, and compounding with, PIT score. TTR12 serves as a prognostic and potential OS surrogate marker, supporting stratification of new risk groups and need for their differential treatment.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
