[Bendamustine, vincristine, prednisolone (BOP) in therapy of advanced low-grade non-Hodgkin lymphoma]]

Low grade non-Hodgkin lymphomas (l-NHL) are rarely showing complete or sustained remissions to conventional chemotherapy. Thus, many therapeutic strategies try to improve the remission rates and outcome in relapsed and refractory l-NHL. Bendamustine (B) is a non-cross resistant alkylating agent shown to be highly effective in lymphoproliferative and other malignant diseases. In an open phase-II study we evaluated the efficacy and toxicity of B in combination with vincristine (O) and prednisolone (P) in heavily pretreated relapsed or refractory l-NHL.

22 patients (median age 61.5 years, range 39-77 years) with relapsed or refractory low grade NHL: immunocytoma (IC) n = 11, centroblastic-centrocytic (CB-CC) n = 6, centrocytic (CC) n = 2, others n = 3, were treated with BOP as follows: patients up to 75 years: 60 mg/m2 B for 5 days; patients over 75 years: 50 mg/m2 B for 5 days. All patients received 2 mg vincristine (O) on day 1, 100 mg/m2 prednisolone (P) on day 1-5; repetition day 29. Prior to BOP patients were pretreated with 1-4 chemotherapy protocols. An average of 5 courses of BOP were administered (range 2-8). In most patients BOP was followed by a maintenance therapy (IFN-alpha n = 11, chlorambucil n = 4, etoposide n = 2).

Objective remission was achieved in 19/22 (86%) patients, complete remission (CR) in 10/22 (45%), partial remission (PR) in 9/22 (41%) and no change (NC) in 3/22 (14%) patients. The mean duration of remission was 16.1 months. Predominant features of side effects of the BOP protocol were myelotoxicity of WHO grade III/IV in 8 of 109 cycles leukopenia (8%), thrombocytopenia 3 cyles (3%) and anaemia in 4 cycles (4%). We observed one WHO grade IV infectious episode. Other side effects were mild and rare. There was a decline of the CD4/8 in more than 50% of patients. However, these changes were not accompanied by a higher rate of infectious episodes.

Salvage therapy of refractory and relapsed l-NHL with BOP results in a high objective remission rate. Together with a maintenance therapy most patients achieved a long-term disease-free survival. Myelotoxicity and the inversion of the CD4/CD8 ratio were frequently observed side effects.