High rates of long-lasting remissions after 5-day bendamustine chemotherapy cycles in pre-treated low-grade non-Hodgkin's-lymphomas

Purpose: Since continuous relapse rates are characteristic for advanced low-grade non-Hodgkin's lymphomas (NHL), their treatment remains a problem. Previous phase II studies showed that bendamustine induced high remission rates in pre-treated low-grade NHL. To further examine its efficacy and side effects, bendamustine has been studied in a large number of patients with pre-treated low-grade NHL. Follow-up time was 3-8 years. Methods: From 1993 to 1998, 102 patients with pre-treated low-grade NHL [histologic subtypes: CLL n = 15, immunocytic n = 46, multiple myeloma (MM) n = 25, others n = 16] received a median of four (range 1-11) 5-day cycles of daily 60 mg/m(2) bendamustine as salvage chemotherapy. Bendamustine was given in short i.v. infusions mainly at intervals of 46 weeks. Results: Partial and complete remissions were observed in 76.5% and disease stabilization in 19.6% of the patients. Only 3.9% showed progressive disease. Median duration of response was 39 months for the NHL patients and 17 months for the MM patients. Median survival time was 32 months for the CLL patients, 31.5 months for the NHL patients and 17.5 months for the MM patients. Non-haematological side effects consisted mainly in reversible reduction of performance status, loss of appetite, and nausea/vomiting and diarrhoea, which were of WHO grade III/IV in less than 5% of patients. Haematological toxicities of WHO grade III/IV have been observed in 6.9%, 11.8%, and 24.5% of patients for hemoglobin, thrombocytes, and leukocytes, respectively. Alopecia did not occur. Febrile episodes or bacterial as well as viral, particularly opportunistic, infections were not observed, although bendamustine induced profound and long-lasting lymphocytopenias, including CD4+-, CD8+-, CD19+-, B-lymphocytes, and NK-cells. Conclusions: Bendamustine proved to be very effective in pre-treated low-grade NHL patients by inducing high rates of long-lasting remissions. Bendamustine combines the pharmacological properties of an alkylating agent with those of a purine analogue and showed no cross-resistance to chlorambucil, melphalan, cyclophosphamide, mitoxantrone, and other anthracyclines. The myelosuppressive toxicities were dose limiting, and the non-haematological side effects were moderate.