Safety and efficacy phase I/II study of forodesine in Japanese patients with relapsed PTCL

On 5^th July 2018, a paper was published in Annals of Hematology by Dai Maruyama, Department of Hematology, National Cancer Center Hospital, Tokyo, Japan, and colleagues, on a phase I/II study of the use of forodesine in patients with relapsed peripheral T-cell lymphoma (PTCL).

Study Overview

• This study was multi-center across 21 sites in Japan between January 2013 and February 2017
• In the phase I portion of the study, 3 patients with R/R PTCL completed the 28-day cycle of 300 mg forodesine twice daily and did not experience dose-limiting toxicity
• 44 patients were treated in the phase II portion of the study. 68% were male and the median age was 69 years (range, 32–79)
  • Patients with PTCL-NOS = 46%
  • Patients with angioimmunoblastic T-cell lymphoma (AITL) = 40%
• The primary endpoint was objective response rate (ORR)
• Secondary endpoints included; duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety

Key Findings

• 41 patients were evaluable for efficacy
• The ORR was 25% (90% CI, 14–38%)
  • ORR for patients with PTCL-NOS = 23% (95% CI, 8–45%)
  • ORR for patients with AITL = 35% (95% CI,13–59%)
• Median DOR = 10.4 months (95% CI, 5.9–16.0 months)
• Median PFS = 1.9 months (95% CI, 1.8–4.6 months)
• Median OS = 15.6 months (95% CI, 10.7–not reached months)
• The most frequent adverse events grade ≥3 included; lymphopenia (n = 46), leukopenia (n = 20), neutropenia (n = 17), thrombocytopenia (n = 12) and anemia (n = 11)

The authors concluded that forodesine showed promising activity with durable responses in patients with PTCL. In addition, they noted that forodesine had an acceptable and manageable safety profile. The data from this study led to the approval of forodesine for patients with R/R PTCL by the Ministry of Health, Labor and Welfare in Japan on 03 April 2017.