Phase II Trial of R-CVP Followed By Rituximab Maintenance Therapy for Patients with Advanced Stage Marginal Zone Lymphoma- Consortium for Improving Survival of Lymphoma (CISL) Study

BACKGROUND:

According to our prior prospective phase II trial, Rituximab in combination with chemotherapy (R-CVP) has been shown to improve response rate (RR) and progression free survival (PFS) in patients with advanced stage marginal zone lymphoma (MZL) compared with chemotherapy alone (CVP). In spite of better RR and PFS, relapses seem to continue after immunotherapeutic treatment in these patients. Thus, eventual relapse remains an important clinical issue for the majority of patients with indolent lymphoma, and defining further ways to extend the period of remission remains an essential goal. But data from clinical trials evaluating rituximab maintenance treatment in these patients are almost limited. We aimed to evaluate the effect of maintenance treatment with rituximab on the PFS of patients with MZL.

METHODS:

Histologically confirmed advanced stage MZL patients who did not progress at the end of 6~8 cycles of 1^st line Rituximab-CVP (cyclophosphamide 750 mg/m² and vincristine 1.4 mg/m² (maximum 2.0 mg), given intravenously on day 1, and oral prednisolone 100 mg on days 1-5) regimen were enrolled. Patients received 2 years of rituximab maintenance therapy (375 mg/m² every 8 weeks). Primary objection was three year progression free survival. This trial is registered with ClinicalTrials.gov, number NCT012113095.

RESULTS

Between March 2010 and March 2013, a total of 47 patients were enrolled with informed consent at this trial from 17 institutes in Korea. Among these patients, 1 patient withdrew informed consent, 1 patient was screening failure with combined thyroid cancer. The median age of the evaluated 45 (32 males, 13 females) patients is 54 (range 33-77) years. Fifteen patients (33.3%) evidenced nodal MZL, 30 (66.7%) extranodal MZL (10 patients were lung, 6 ocular, and 5 stomach, in order of frequency). The IPI score were 1 in 13 (28.9%), 2 in 21 (46.7%), 3 in 9 (20%), and 4 in 2 (4.4%) patients. The patients received a total of 6 or 8 cycles of 1^st line R-CVP chemotherapy were 10 (22.2%) and 35 (77.8%), respectively. There were 20 CR (44.4%), 22 PR (48.9%), and 3 SD (6.7%). Median treated number of rituximab maintenance followed by R-CVP was 12 (range 1-12). Thirty two patients (71.1%) patients completed planned 12 cycles of rituximab maintenance. Disease progression during rituximab maintenance was 8 patients, 2 patients stopped treatment because of side effects (1 abdominal pain, 1 recurrent pneumonia) 2 patients were follow-up loss. Four patients were expired (each 1 pneumonitis, pneumonia, sepsis, and disease progression). PFS and OS rate at 3 years were 78.9% and 90.6%, respectively.

CONCLUSION: 2 years of rituximab maintenance therapy after R-CVP first-line chemotherapy for advanced stage MZL might be improve PFS with tolerable toxicities