Phase I/II Multicenter Study of Romidepsin in Japanese Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma

Introduction: Peripheral T-cell lymphoma (PTCL) is an aggressive lymphoma associated with poor prognosis. There is no consensus on standard therapy, and options are limited for patients with relapsed/refractory (R/R) disease. Romidepsin, a potent histone deacetylase inhibitor, has US FDA approval for patients with >=1 prior treatment for PTCL based on 25%-38% overall response rates (ORR) and durable responses (Piekarz et al, Blood. 2011;117:5827; Coiffier et al, J Clin Oncol. 2012;30:631). Here we report results from the phase I/II, multicenter, open-label study of romidepsin in Japanese patients with R/R PTCL or cutaneous T-cell lymphoma (CTCL) (TCL-001; NCT01456039). Methods: Patients aged >=20 years with R/R PTCL or CTCL received romidepsin via a 4-hour IV infusion on days 1, 8, and 15 of each 28-day cycle until progressive disease or unacceptable toxicity. The phase I portion of the study used a 3+3 design to identify any dose-limiting toxicity (DLT; phase I primary endpoint) with romidepsin 9 mg/m2 (cohort 1) and 14 mg/m2 (cohort 2). The phase II dose was based on the highest dose where =1 day. Assessments of the intent-to-treat (ITT) population included all patients receiving at least 1 dose of romidepsin. Results: The ITT population comprised 48 patients with PTCL and 2 with CTCL (1 each in the 9 and 14 mg/m2 cohorts). The common PTCL subtypes were angioimmunoblastic T-cell lymphoma (AITL, n=21, 44%), PTCL not otherwise specified (PTCL-NOS, n=20, 42%), and anaplastic large-cell lymphoma (ALCL ALK-1 negative, n=3, 6%). Most patients had a favorable ECOG performance status (86% 0-1) and 72% were >=65 years of age. Patients had received a median of 2 prior therapies (range, 1-9). Of 9 patients assessable in phase I (n=3 at 9 mg/m2 and n=6 at 14 mg/m2), none experienced a DLT. The recommended phase II dose was 14 mg/m2 in 40 subsequently treated patients. The overall population received a median of 10 doses (range, 1-135) for a median treatment duration of 12.9 weeks (range, 0.1-184.3; 8 patients were treated for >=36 weeks). The common all-grade adverse events (AEs) were thrombocytopenia (n=49, 98%), lymphopenia (n=44, 88%), leukopenia (n=42, 84%), neutropenia (n=40, 80%), pyrexia (n=33, 66%), dysgeusia (n=31, 62%), decreased appetite (n=28, 56%), and nausea (n=27, 54%). The common grade >=3 AEs were lymphopenia (n=37, 74%), neutropenia (n=27, 54%), leukopenia (n=23, 46%), and thrombocytopenia (n=19, 38%). Of the 39 patients whose CD4+ T-cell counts were monitored, while decreased CD4+ T-cell counts ( Among the 40 patients with PTCL (phase II), the ORR was 43% (95% CI, 27%-58%), including 10 patients (25%) with complete response (CR) or CR unconfirmed (CRu) and 7 (17%) with partial responses (PR) (Table 1). The obtained ORR was significantly higher compared with the threshold ORR of 10% (P Conclusions: Results from this phase I/II study identified a tolerable dose of romidepsin and indicated that romidepsin has an acceptable toxicity profile with clinically meaningful, efficacy in Japanese patients with R/R PTCL. The efficacy and safety data were comparable with results from other romidepsin phase II studies. Disclosures Ogura: Celltrion, Inc.: Consultancy, Honoraria; SymBio Pharmaceuticals: Consultancy, Honoraria. Maruyama:Janssen: Honoraria; Takeda: Honoraria. Tobinai:Chugai Pharma: Research Funding; Daiichi Sankyo Co., Ltd.: Consultancy; Mundipharma KK: Honoraria, Research Funding; SERVIER: Research Funding; HUYA Bioscience: Honoraria; Celgene: Research Funding; Kyowa Hakko Kirin: Research Funding; GlaxoSmithKline: Research Funding; Janssen Pharmaceuticals: Honoraria, Research Funding; Abbvie: Research Funding; Takeda: Honoraria, Research Funding; Zenyaku Kogyo: Honoraria; Eisai: Honoraria, Research Funding; Ono Pharmaceutical: Research Funding. Uchida:SymBio Pharmaceuticals: Research Funding. Hatake:Chugai: Research Funding; Meiji-Seika: Consultancy; Otsuka: Consultancy; Kyowa Kirin: Honoraria, Research Funding. Tsukasaki:Daiichi Sankyo Co., Ltd.: Consultancy; Takeda: Research Funding. Ishida:Celgene KK: Research Funding; Kyowa Hakko Kirin, Co., Ltd.: Honoraria, Research Funding; Bayer Pharma AG: Research Funding. Ishizawa:SymBio Pharmaceuticals: Research Funding. Laille:Celgene: Employment, Equity Ownership. Ro:Celgene: Employment, Equity Ownership. Tamakoshi:Celgene: Employment, Equity Ownership. Sakurai:Celgene: Employment. Ohtsu:Celgene: Employment, Equity Ownership.