Acute Toxicity of Mitoxantrone, Chlorambucil and Prednisolone (MCP) versus MCP plus Rituximab in Low-Grade Non-Hodgkin’s Lymphoma – Interim Results of a Phase III Trial

Background: Phase I and II studies utilizing the chimeric anti-CD 20 antibody rituximab demonstrate good results in relapsed and resistant follicular and low-grade lymphoma; in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy excellent remission rates and survival data have been achieved. These data justify to evaluate the efficacy and toxicity of a combination of chemotherapy and rituximab in comparison to standard chemotherapy alone in a prospective randomized trial. Included in this study are untreated patients with advanced follicular lymphoma (FCL grades I and II) and lymphoplasmocytoid lymphoma as well as mantle cell lymphoma stages III and IV. According to the results of phase I and II trials we expect a better quality of remissions resulting in an improved freedom from treatment failure (FFTF) and survival in the experimental arm of the study. Material and Methods: In this trial, MCP (mitoxantrone 8 mg/m 2 , days 1+2, chlorambucil 3 × 3 mg/m 2 , days 1–5, and prednisolone 25 mg/m 2 , days 1–5, q4 weeks × 8) is compared with the combination of rituximab (R) (375 mg/m 2 , day 1) and MCP (days 3–7) q4 weeks × 8. In an interim analysis of 30 patients, 15 in each treatment group, the acute toxicity of 52 and 50 matched cycles of MCP and MCP+R, respectively, were evaluated. Both patient groups are comparable. Results: Counting all adverse events (CTC grades 1–4) there are 36 events in the MCP+R arm and 14 in the MCP arm. If only adverse events of CTC grades 3 and 4 are analyzed, however, the differences are much less pronounced; only 6 patients in each group had leukopenia or thrombocytopenia of grade 3 or 4. When comparing treatment cycles, myelotoxicity (CTC grades 3 and 4 concerning leukocytes and CTC grades 2–4 for platelets) occurred in 17/50 MCP+R cycles but in only 9/52 MCP cycles. Conclusion: Our preliminary data regarding acute toxicity suggest a tendency to more adverse events in the experimental arm (MCP+R) of our study. In the cohort of patients analyzed we did not observe severe infusion-related events in the patients who were treated with rituximab.