Table 1.

Selected novel agents that have been studied for treatment of PTCLs in the frontline or relapsed/refractory settings

Drug(s)Mechanism
Brentuximab vedotin (SGN-35) Antibody-drug conjugate consisting of a chimeric anti-CD30 monoclonal antibody linked to cytotoxic agent monomethyl auristatin E 
Pralatrexate Selective antifolate analogue inhibiting dihydrofolate reductase, resulting in dysregulated purine and pyrimidine synthesis 
Romidepsin, belinostat, vorinostat Histone deacetylase inhibitors (interfere with histone and chromatin modification) 
Lenalidomide Immunomodulatory agent enhancing ubiquitin ligase activity and proteasomal degradation of disease-specific proteins 
Azacitidine DNA hypomethylating agent (decrease the amount of cellular DNA methylation, allowing for tumor suppressor gene expression) 
Duvelisib, linperlisib, tenalisib Oral dual inhibitor of phosphatidylinositol 3-kinase (PI3K)-δ and/or PI3K-γ isoforms 
Tazemetostat, valemetostat, tulmimetostat, HH2853 Small molecules inhibiting histone methyltransferase activity of EZH1/2 (dual inhibitors) or EZH2 alone 
Ruxolitinib, golidocitinib Janus kinase (JAK) inhibitors interfering with dysregulated cytokine signaling 
Crizotinib, alectinib Oral small-molecule tyrosine kinase inhibitor with binding specificity for ALK and ROS1 
Soquelitinib (CPI-818) Oral small-molecule irreversible inhibitor of interleukin-2 inducible T-cell kinase (ITK) disrupting T-cell receptor signaling through ITK-mediated signal transduction 
Drug(s)Mechanism
Brentuximab vedotin (SGN-35) Antibody-drug conjugate consisting of a chimeric anti-CD30 monoclonal antibody linked to cytotoxic agent monomethyl auristatin E 
Pralatrexate Selective antifolate analogue inhibiting dihydrofolate reductase, resulting in dysregulated purine and pyrimidine synthesis 
Romidepsin, belinostat, vorinostat Histone deacetylase inhibitors (interfere with histone and chromatin modification) 
Lenalidomide Immunomodulatory agent enhancing ubiquitin ligase activity and proteasomal degradation of disease-specific proteins 
Azacitidine DNA hypomethylating agent (decrease the amount of cellular DNA methylation, allowing for tumor suppressor gene expression) 
Duvelisib, linperlisib, tenalisib Oral dual inhibitor of phosphatidylinositol 3-kinase (PI3K)-δ and/or PI3K-γ isoforms 
Tazemetostat, valemetostat, tulmimetostat, HH2853 Small molecules inhibiting histone methyltransferase activity of EZH1/2 (dual inhibitors) or EZH2 alone 
Ruxolitinib, golidocitinib Janus kinase (JAK) inhibitors interfering with dysregulated cytokine signaling 
Crizotinib, alectinib Oral small-molecule tyrosine kinase inhibitor with binding specificity for ALK and ROS1 
Soquelitinib (CPI-818) Oral small-molecule irreversible inhibitor of interleukin-2 inducible T-cell kinase (ITK) disrupting T-cell receptor signaling through ITK-mediated signal transduction 

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