A trial has found that patients with an aggressive subtype of non-Hodgkin’s lymphoma are likely to benefit from an epigenetic drug, US researchers have reported.
The drug, azacitidine, is currently used in the US for myelodysplastic syndrome and some leukaemias. It prevents the addition of chemical changes to DNA called methylation. Many tumours have dense patches of these chemical changes – known as ‘hypermethylation’ – which reduce the cells’ ability to control tumour growth.
In this multi-centre study, a team led by Dr Jia Ruan of Weill Cornell Medical Center, New York, USA, gave oral azacitidine to 20 patients with peripheral T-cell lymphomas, alongside the standard chemotherapy regimen CHOP.
After six cycles of the azacytidine-CHOP combination, complete response was seen in 75% of the patients. 17 patients with the ‘T-follicular helper’ (TFH) phenotype had an even higher complete response rate of 88.2%.
After two years, progression-free survival was estimated to be 66% and nearly 70% for those with the TFH phenotype. Overall survival was 68%, and 76% for those with the TFH phenotype.
The drug appeared to alter the tumour’s genetic microenvironment, upregulating genes related to natural cell death.
In the journal Blood, the authors explain that peripheral T-cell lymphomas are relatively hard to treat successfully and have an estimated five-year survival rate of only 20% to 30%.
They write: “Peripheral T-cell lymphomas with T-follicular helper phenotype has recurrent mutations affecting epigenetic regulators, which may contribute to aberrant DNA methylation and chemoresistance.”
Dr Ruan said: “The treatment shows promise for this T cell lymphoma subtype, and we look forward to seeing how it performs in a larger clinical trial.”
A smaller study published last year by co-author Dr Peter Martin also found that this combination therapy boosted complete response rates for patients with certain aggressive B-cell lymphomas.
Ruan J, Moskowitz A, Mehta-Shah N, Sokol L, Chen Z, Kotlov N, Nos G, Sorokina M, Maksimov V, Sboner A, Sigouros M, van Besien K, Horwitz S, Rutherford SC, Mulvey E, Revuelta MV, Xiang J, Alonso A, Melnick A, Elemento O, Inghirami G, Leonard JP, Cerchietti L, Martin P. (2023) “Multicenter phase 2 study of oral azacitidine (CC-486) plus CHOP as initial treatment for PTCL.” Blood, doi: 10.1182/blood.2022018254
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