ERFURT, Germany—Interim data from a randomized phase III study show that MCP (mitoxantrone [Novantrone], chlorambucil(Drug information on chlorambucil) [Leukeran], prednisolone(Drug information on prednisolone)) with or without rituximab(Drug information on rituximab) (Rituxan) is active in advanced indolent lymphomas. Michael Herold, MD, reporting for the Ostdeutsche Studiengruppe Haematologie/Oncologie (OSHO), said, "The response rate of 81% is within the range of that seen with standard therapies. The complete response (CR) rate of 40% was highly encouraging, particularly given the multi-institutional setting of this study. To date, no significant change in response has been seen with the addition of rituximab to MCP, but further follow-up is needed to determine if the addition of rituximab will improve the duration of response."
More than 270 patients have been randomized in this prospective study, and investigators expect to complete accrual of 320 patients within the next few months. Study end points are response rate, time to treatment failure, survival, and safety. The study is open to patients with advanced follicular lymphoma (grade 1 or 2), lymphoplasmacytic lymphoma, or mantle cell lymphoma (stage III or IV).
Study Design
Patients are randomized either to rituximab (375 mg/m², day 1) plus MCP (mitoxantrone at 8 mg/m² , days 3 and 4, chlorambucil at 3 mg/m² tid, days 3-7, prednisolone at 25 mg/m², days 3-7) every 4 weeks × 8, or to MCP alone (days 1-5) every 4 weeks × 8.
"According to the results of phase I and II trials we expect better quality remissions, in particular higher CR rates, resulting in improved freedom from treatment failure and survival in the experimental arm of the study," Dr. Herold said.
Interim Analysis
This interim analysis was based on data for 106 patients who were evaluable on an intent-to-treat basis—55 in the rituximab plus MCP group and 51 in the MCP group. Dr. Herold reported that the response rate (CR plus PR) for all patients is 81% (95% confidence interval: 72%-88%), and that at present there is no statistically significant difference between the treatment arms, so the respective numbers are still blinded. The CR rate for all patients is 40%, and the PR rate is 41%.
For follicular lymphoma patients (n = 62), the response data are even more impressive: the CR rate of 47% exceeds the PR rate of 39%, giving an overall response rate of 86%.
Toxicity analysis was made on the basis of 414 cycles in the rituximab plus MCP group and 347 cycles in the MCP group (7.5 vs 6.8 per patient). There was a tendency to more adverse events in the rituximab plus MCP group (375 vs 266; 0.9 vs 0.76 per cycle), but this was not statistically significant (P = .612).
Myelotoxicity is the main cause for Common Toxicity Criteria (CTC) grade 4 toxicity, and a significantly higher proportion of CTC grade 4 leukopenia occurred in the rituximab plus MCP group (13% vs 6% of cycles, P = .008). This did not result in an increased frequency of infections or in reduced chemotherapy dose intensity.
"Our preliminary response data demonstrate an overall response rate comparable to or even better than other multicenter studies, with a remarkably high proportion of complete responses for the entire group of patients. Regarding toxicity, there is a tendency to more adverse events in the rituximab plus MCP group, but this had no impact on infections or dose intensity of chemotherapy, and we have had no severe infusion-related events following rituximab," Dr. Herold said.
