Bendamustine: inadequate or outdated data.

Chronic lymphocytic leukaemia (the most common form of leukaemia in adults), non-Hodgkin's lymphoma and multiple myeloma are haematological malignancies. Their clinical course varies from one patient to another. Bendamustine (Levact, MA holder Astellas, French representative: Mundipharma), an alkylating agent, was authorised for first-line treatment of chronic lymphocytic leukaemia and multiple myeloma, and for second-line single-agent treatment of indolent non-Hodgkin's lymphoma. Most data on the efficacy of bendamustine as first-line treatment for chronic lymphocytic leukaemia come from a randomised unblinded trial comparing bendamustine versus chlorambucil in 312 patients. The trial was stopped prematurely (which tends to overestimate the benefits) after a median follow-up of 35 months. Median overall survival did not differ between the groups but the length of follow-up was inadequate, given the slow course of the disease. Median progression-free survival was statistically significantly longer with bendamustine (21.5 months versus 8.3 months). The overall response rate was also statistically significantly higher with bendamustine (68% versus 31%). An indirect comparison (there are no head-to-head comparisons) suggests that these results are similar to those obtained with fludarabine. In indolent non-Hodgkin's lymphoma, assessment of bendamustine is mainly based on a single uncontrolled trial. No data on overall survival were reported, ruling out conclusions as to the possible benefits of bendamustine. In multiple myeloma, assessment of bendamustine is based on an unblinded trial of bendamustine + prednisone versus melphalan + prednisone in 131 patients. This trial took place before the value of thalidomide in this setting had been shown. In addition, it suffered from many methodological flaws (study population, endpoints, etc.). Bendamustine had no advantages over melphalan. Bendamustine has many serious and potentially life-threatening adverse effects, including frequent myelosuppression, infections, and secondary cancers. In practice, the efficacy of bendamustine in non-Hodgkin's lymphoma and multiple myeloma is uncertain, while its adverse effects are numerous, varied and often severe. Further trials are needed to determine the value of bendamustine in chronic lymphocytic leukaemia.