Combined Oral 5-AzacytidineaAnd Romidepsin are Highly Effective in Patients with PTCL: A Multicenter Phase 2 Study

Combined Oral 5-AzacytidineaAnd Romidepsin are Highly Effective in Patients with PTCL: A Multicenter Phase 2 Study

Certain cancers are susceptible to epigenetic modifiers, and in particular peripheral T-cell lymphomas are an important subset.  In vitro synergism between histone T-cell acetylase inhibitors and DNA methyltransferase inhibitors have been well documented in preclinical models of T-cell lymphoma. In the April 22, 2021 edition of the journal Blood, investigators report on the role of combined oral 5-azacytidine and romidepsin in peripheral T-cell lymphomas, as a phase 1 clinical trial. Oral 5-azacytidine and romidepsin were shown to be safe and efficacious with lineage selective activity in patients who have relapsed / refractory peripheral T-cell lymphoma and hence this trial was developed. 

Patients who were treatment naïve or had relapsed / refractory disease received azacitidine 300 mg once daily on days 1-14 as well as romidepsin 14 mg/m² on days 8, 15 and 22 on a 35-day cycle.  The primary objective was overall response rate. Targeted next generation sequencing was also performed on tumor tissue.  This was used to correlate mutation profiles and response rates.  Of the 25 patients who were enrolled in the study, the overall response rate and complete response rates were 61% and 48%, respectively.  Patients with T follicular helper cell phenotype exhibited higher response rates that 80% in a complete remission rate of 67%.  The most common grade 3 adverse event was thrombocytopenia, 48% with neutropenia , 40%, lymphopenia , 32% and anemia , 16%.  After a median follow-up of 13.5 months, the median PFS, duration of response and overall survival were 8 months, 20.3 months and not reached. 

The median progression free survival and overall worse survival were 8 months and 20.6 months, respectively in patients with relapsed / refractory disease.  Patients with the tTFH phenotype had a particularly long median survival, median not reach.  Responders with a high average number of mutations in genes involving DNA methylation and histology is a release were better responders. 

The authors concluded ” combined azacitidine and romidepsin are highly active in PCL patients and can serve as a platform for novel regimens in this disease.”