Background: Epigenetic manipulation and immunomodulation are therapeutic strategies in hematologic malignancies. Romidepsin (romi), a histone deacetylase inhibitor, and lenalidomide (len), an immunomodulatory agent, both have efficacy and lack cumulative toxicity in relapsed/refractory (rel/ref) lymphoma and myeloma. Methods: The phase I part of the study was reported at ASCO 2014. The MTD defined in cycle 1 was romi 14 mg/m² IV on days 1, 8, and 15 and len 25 mg oral on days 1-21 of a 28-day cycle. Patients (pts) were treated to progression or intolerance. Disease-specific cohorts in T-cell lymphoma (TCL), B-cell lymphoma and multiple myeloma were enrolled at the MTD. We report the results of the TCL subjects.Results: 21 pts with TCL (10 CTCL, 11 PTCL) were enrolled with 15 treated at the MTD. Median age was 64 with 52% male (n = 11).19 pts were evaluable for efficacy with an ORR of 53% (10/19). Two pts were not evaluable for response (one due to toxicity in cycle 1 without progression, one on steroids for idiopathic thrombocytopenic purpura with PET normalization prior to dose 1). The ORR in PTCL was 50% (5/10, 5 PR). Responses were seen in PTCL-NOS (3), AITL (1), T-PLL (1). One with relapsed ATLL remains on therapy with SD ongoing at 24 weeks (w). The ORR in CTCL was 56% (5/9, 2 CR, 3 PR). CR was seen in transformed MF (1), and Sezary syndrome (1). The median time to response was 7.3 w (range: 2.8-16.9 w). Median OS was not reached. Median event free survival was 15.5 w (CTCL 30.0 w, PTCL 13.5 w). However 48% (10/21) pts remain on therapy (2 CR, 6 PR, 2 SD) at a median of 15.3 w (range: 9.0-106.6 w). 7 pts discontinued for progression, 3 for toxicity and 1 for transplant. The median number of cycles was 4 (range: 1-27). 71% of pts had AEs ≥ Grade 3, with the most common ( ≥ 10%) being neutropenia (48%), thrombocytopenia (38%), anemia (33%), electrolyte abnormalities (K, Phos, glucose, Mg) (43%). Conclusions: The combination of romi and len appears to have significant activity in rel/ref TCL (ORR 53%) with acceptable safety profile. These results support further evaluation of romi and len in patients with TCL, including additional studies in both CTCL and PTCL. Clinical trial information: NCT01755975