An expanded-access clinical study of thiotepa (DSP-1958) high-dose chemotherapy before autologous hematopoietic stem cell transplantation in patients with malignant lymphoma.

Thiotepa, an antineoplastic ethylenimine alkylating agent that can penetrate the central nervous system, was recently approved in Japan as high-dose chemotherapy prior to autologous hematopoietic stem cell transplantation (HSCT) for patients with malignant lymphoma. To further evaluate the safety and efficacy of thiotepa, a multicenter, open-label, non-comparative, expanded access program was undertaken in Japan, including a larger population of Asian patients with malignant lymphoma. Intravenous thiotepa (200 mg/m2/day) was administered over 2 h on days -4 and -3 before scheduled HSCT, plus intravenous busulfan (0.8 mg/kg) over 2 h every 6 h on days -8, -7, -6 and -5. In the safety analysis population (N = 51), 25 patients (49.0%) had primary central nervous system lymphomas. The most common treatment-emergent adverse event was febrile neutropenia (49/51 [96.1%]). No unexpected safety events were observed, and no event resulted in death or treatment modification. Forty-seven patients (92.2%) had engraftment (neutrophil count ≥ 500/mm3 for three consecutive days after bone-marrow suppression and HSCT). The survival rate at day 100 post-transplantation was 100%. These data confirm the safety of thiotepa prior to autologous HSCT for patients with malignant lymphoma. Trial registration: JapicCTI-173654.