Phase II study of the novel antifolate agent pralatrexate in combination with the histone deacetylase inhibitor romidepsin for the treatment of patients with mature T-cell lymphoma

Abstract

Previously, we conducted a Phase I study of the combination of pralatrexate and romidepsin in patients with relapsed/refractory (R/R) lymphomas and subsequently conducted a multicenter Phase II study in patients with untreated or R/R mature T cell lymphomas (MTCL). Patients received pralatrexate 25 mg/m² and romidepsin 12 mg/m² every 2 weeks. Fourteen patients were evaluable for efficacy. Overall response rate was 35.7% with CR in 14.3% and disease control in 50%. The mDOR was 8.2 months, mPFS was 3.6 months, and mOS was 20.2 months. Gastrointestinal side effects were most common in up to 33%; there was only one hematologic toxicity of grade 3 anemia. Combining results of MTCL patients from the Phase I and II studies (N = 28), the ORR was 53.5% with CR in 21.4%, disease control in67.8%, and DOR of 7.2 months. The combination was safe however does not out-perform other combination strategies.Trial Registration: www.clinicaltrials.gov (NCT 01947140).

Keywords:

• Chemotherapeutic approaches
• lymphoma and Hodgkin disease
• clinical results
• T-cell lymphoma
• epigenetics
• antifolate

Authors’ contributions

YKRT: Analysis, interpretation of results, draft manuscript preparation. SJ, SKB, AS, JKL, MMF: Data collection. ST: Analysis and draft manuscript preparation. BE: Analysis. BP: Supervision. JEA: Conceptualization, design, methodology and project administration, funding acquisition, data collection and analysis, manuscript preparation. All authors reviewed the results and approved the final version of the manuscript.

Disclosure statement

SJ: SRA with Acrotech; SKB: Consulting for Acrotech, Affimed, Daiichi Sankyo, Janssen, Kyowa Kirin, Research Support from Calgene, Seagen; JKL: Consulting for Epizyme and Merck; AS: Honorarium and Speaker: Acrotech, Daiichi Sankyo, Kite, Seagen; Employment; Flatiron Health; Stock: Roche; BP: Honoraria Takeda, Seagen; JEA: Advisory Board: AstraZeneca, Incyte; Honorarium: Epizyme.

Additional information

Funding

The authors acknowledge support from the Herbert Irving Scholar Program UL1 TR001873 (JEA) and The Esther and Oded Aboodi Lymphoma Research Fund (JEA), American Society of Hematology Research Training for Fellow Award (YKRT and ST) and Conquer Cancer American Society of Clinical Oncology Young Investigator Award (YKRT).