Darinaparsin in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of an Asian Phase 2 Study.

Darinaparsin is a novel organic arsenical compound of dimethylated arsenic conjugated to glutathione, with antitumor activity and a mechanism of action markedly different from other available agents. This phase II, nonrandomized, single-arm, open-label study evaluated the efficacy and safety of intravenous darinaparsin (300 mg/m2 over 1 hour, once daily for five consecutive days, per 21-day cycle) and its pharmacokinetics at multiple doses in 65 Asian patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). The primary endpoint was the overall response rate (ORR). The ORR based on central assessment was 19.3% (90% confidence interval: 11.2-29.9%), which was significantly higher than the predefined threshold of 10% (p = 0.024). The ORR was 16.2% in patients with PTCL-not otherwise specified and 29.4% in patients with angioimmunoblastic T-cell lymphoma. The tumor size decreased in 62.3% of patients. Treatment-emergent adverse events (TEAEs) were observed in 98.5% of patients. Grade ≥3 TEAEs with an incidence rate ≥5% included anemia (15.4%), thrombocytopenia (13.8%), neutropenia (12.3%), leukopenia (9.2%), lymphopenia (9.2%), and hypertension (6.2%). Darinaparsin is effective and well tolerated, with TEAEs that were clinically acceptable and manageable with symptomatic treatment and dose reductions (ClinicalTrials.gov: NCT02653976).