ERFURT, GermanyInterim data from a randomized phase III
study show that MCP (mitoxantrone [Novantrone], chlorambucil [Leukeran],
prednisolone) with or without 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).
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
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.
This interim analysis was based on data for 106 patients who
were evaluable on an intent-to-treat basis55 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.