A global retrospective study has offered fresh insights into optimising treatment for patients with relapsed or refractory T-cell and natural killer-cell lymphomas, rare and aggressive cancers with no established standard of care.
Using data from the PETAL global cohort, researchers evaluated overall survival outcomes across 12 treatment sequences involving cytotoxic chemotherapy (CC), epigenetic modifiers (EM), and small molecule inhibitors (SMI) in second- and third line (2L and 3L) settings. The study, designed as a ‘target trial,’ adjusted for key clinical variables including age, lymphoma subtype, disease refractoriness, and prognostic scores.
Among 540 patients receiving 2L therapy and 290 receiving 3L, the combination of 2L SMI followed by 3L EM was associated with significantly improved overall survival compared to repeated chemotherapy (adjusted hazard ratio [aHR]: 0.29; 95% CI: 0.11–0.74; p=0.010). This sequence outperformed most other treatment strategies.
Notably, patients with angioimmunoblastic T-cell lymphoma benefited significantly from 2L SMI compared to both CC and EM, while those in high-risk prognostic groups also showed better outcomes with either SMI or EM over chemotherapy.
The findings, confirmed through multiple analytical approaches including reinforcement learning and causal inference methods, offer a preliminary treatment selection framework. While prospective trials are needed, the data highlight the potential of tailoring second- and third-line therapies based on disease subtype and risk profile to improve survival outcomes in this challenging patient population.
Reference
Sorial MN et al. Forecasting optimal treatments in relapsed/refractory mature T- and NK-cell lymphomas: A global PETAL Consortium study. Br J Haematol. 2025 May 1. doi: 10.1111/bjh.20063.
