Background: Patients with peripheral T-cell lymphoma (PTCL) lack good treatment options, particularly in the relapsed and refractory setting. Our work suggested that epigenetic therapies can be safe and effective for patients with PTCL, particularly those with T-cell lymphomas with a follicular helper (TFH) phenotype. It is thought that recurrent mutations in epigenetic factors, including Ten-Eleven Translocation-2 (TET2), DNA methyl transferase-3A (DNMT3A) and isocitrate dehydrogenase-2 (IDH2) may contribute to PTLC vulnerability to epigenetic drugs. Methods: Objective of this study was to evaluate the merits of romidepsin plus subcutaneous azacitidine in patients with PTCL when administered in a ‘real-world’ scenario. We retrospectively identified 17 PTCL patients world-wide that were treated with azacitidine and romidepsin outside of a clinical trial based upon queries regarding off study use. The study was reviewed and approved by each Medical Center Institutional Review Board. Their pretreatment characteristics are shown in Table. Results: Eleven patients had angioimmunoblastic lymphoma (AITL), 2 had adult T-cell leukemia/lymphoma (ATLL), 2 had TFH PTCL, 1 had PTCL-NOS and 1 had composite lymphoma (TFH PTCL with diffuse large B cell lymphoma). Ten patients had next generation sequencing performed. Most common mutations found were those of TET2 (7 pts), RHOA (4pts), IDH2 (3pts) and DNMT3A (1 pt). One ATLL patient had mutations in TRAF3, FAT1 and MED12. Among these 17 patients, overall response rate (ORR) was 76% and the complete response rate (CR) was 52%. Median number of cycles was 4 (range 1-12). Treatment was well tolerated but notable adverse effects included nausea, fatigue, rash, neutropenia and thrombocytopenia. One patient experienced febrile neutropenia while another had pulmonary infiltrates (differential diagnosis included drug toxicity versus infection). In 4 patients, azacitidine and romidepsin were used to achieve remission prior to allogeneic transplant (range of cycles 1-3), with all 4 patients were in CR at their last disease assessment. Conclusions: Subcutaneous azacitidine and romidepsin administered in a ‘real-world’ situation is highly effective in patients with relapsed PTCL with tolerable toxicity, and can be used to successfully bridge patients to stem cell transplant.