Patients with relapsed or refractory (RR) mature T and NK-cell neoplasms (TNKL) experienced better overall survival (OS) and real-world progression-free survival-2 (rwPFS2) with small molecule inhibitors (SI) as second-line (2L) therapy compared with cytotoxic chemotherapy (CC) as 2L therapy. However, the use of epigenetic modifiers (EM) did not significantly impact these outcomes. These results from an international cohort study were presented at the ASH Annual Meeting 2023.
Subsequent analyses focused on specific patient subgroups based on histology, refractory status, and whether patients underwent allogeneic hematopoietic cell transplantation after 2L therapy. Notably, survival outcomes in patients with angioimmunoblastic T-cell lymphoma (AITL) treated with SI were improved, compared with CC. However, the study did not identify distinct differences in overall survival outcomes across the various sequences of therapy administered.
Despite evolving therapeutic strategies, patients with RR mature TNKL encounter treatment challenges with no universal standard of care. Presently, these patients often navigate multiple therapies without clear guidance on optimal treatment sequences.
In a recent global study spanning 15 centers across 6 continents, researchers investigated survival outcomes in a cohort of patients with RR TNKL, analyzing therapy sequences in a retrospective target-trial cohort study. This updated study cohort included patients who did not have anaplastic large cell lymphoma and had received CC as their first-line therapy or had documented 2L therapy initiation.
The study classified patients based on their 2L therapy into 3 categories: EM, SI, or CC, including antibody-drug conjugates. Outcomes measured OS and rwPFS2 — time from 2L start to fourth line start or death to assess the effect of 2L therapy on the subsequent third-line (3L) treatment.
From the global cohort of 925 patients, this cohort consisted of 472 patients with RR TNKL who exhibited various therapeutic histories and disease characteristics across the EM (n=89), SI (n=46), and CC (n=337) groups at 2L treatment. Among these patients, SI improved OS and rwPFS2 compared with CC, whereas EM did not significantly impact these outcomes.
Further analyses delved into specific subgroups based on histology, refractory status, and allogeneic hematopoietic cell transplantation after 2L therapy, uncovering varying effects on survival outcomes.
Key findings revealed improved survival outcomes in patients with AITL treated with SI at the 2L, compared with CC; however, no distinct differences emerged in overall outcomes across different therapy sequences.
In light of these insights, ongoing efforts are exploring advanced methodologies such as machine learning to unravel the intricate impact of therapy sequences. This study underscores the need for individualized therapy selection based on patient and disease characteristics, as well as drug accessibility, in the pursuit of effective treatments for RR TNKL.
Reference
Sorial MN, Koh MJ, Boussi L, et al. Impact of therapy sequence on survival outcomes among patients with relapsed or refractory mature T and NK cell neoplasms: a global retrospective cohort study. Presented at ASH 2023. December 9-12, 2023. San Diego, CA. Abstract 3080.
