A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma

Jennifer E. Amengual, Renee Lichtenstein, Jennifer Lue, Ahmed Sawas, Changchun Deng, Emily Lichtenstein, Karen Khan, Laine Atkins, Aishling Rada, Hye A. Kim, Codruta Chiuzan, Matko Kalac, Enrica Marchi, Lorenzo Falchi, Mark A. Francescone, Lawrence Schwartz, Serge Cremers and Owen A. O’Connor

Key Points

  • The combination of romidepsin and pralatrexate is safe and well tolerated in patients with relapsed/refractory lymphoma.

  • The combination led to an overall response rate of 71% (10/14, with 4/14 complete responses) in patients with relapsed/refractory T-cell lymphoma.

Publisher's Note: There is a Blood Commentary on this article in this issue.


Peripheral T-cell lymphomas (PTCL) are a group of rare malignancies characterized by chemotherapy resistance and poor prognosis. Romidepsin and pralatrexate were approved by the US Food and Drug Administration for patients with relapsed/refractory PTCL, exhibiting response rates of 25% and 29% respectively. Based on synergy in preclinical models of PTCL, we initiated a phase 1 study of pralatrexate plus romidepsin in patients with relapsed/refractory lymphoma. This was a single institution dose-escalation study of pralatrexate plus romidepsin designed to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetic profile, and response rates. Patients were treated with pralatrexate (10 to 25 mg/m2) and romidepsin (12 to 14 mg/m2) on 1 of 3 schedules: every week × 3 every 28 days, every week × 2 every 21 days, and every other week every 28 days. Treatment continued until progression, withdrawal of consent, or medical necessity. Twenty-nine patients were enrolled and evaluable for toxicity. Coadministration of pralatrexate and romidepsin was safe, well tolerated, with 3 DLTs across all schedules (grade 3 oral mucositis × 2; grade 4 sepsis × 1). The recommended phase 2 dose was defined as pralatrexate 25 mg/m2 and romidepsin 12 mg/m2 every other week. Twenty-three patients were evaluable for response. The overall response rate was 57% (13/23) across all patients and 71% (10/14) in PTCL. The phase 1 study of pralatrexate plus romidepsin resulted in a high response rate in patients with previously treated PTCL. A phase 2 study in PTCL will determine the efficacy of the combination. This trial was registered at as #NCT01947140.

  • Submitted September 15, 2017.
  • Accepted October 30, 2017.
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