Therapeutic approaches to follicular lymphoma (FL) continue to evolve via the incorporation of immunotherapy, novel chemotherapeutics, and stem cell transplantation. The East German Study Group enrolled patients with previously untreated follicular, lymphoplasmacytic, and mantle cell lymphoma in a prospective phase III multicenter trial of MCP (mitoxantrone, chlorambucil, and prednisolone) versus rituximab-MCP. Only the results for the FL patients are reported, with all patients being stage III-IV, grade 1 or 2, and in need of therapy based upon “B” symptoms and disease volume or progression. Virtually all patients had intermediate- or high-risk FLIPI prognostic scores. Treatment was administered in 28-day cycles with a total of eight cycles for patients in complete (CR) or partial remission (PR) following cycle 6. All responding patients received interferon alfa-2a thrice weekly as maintenance therapy, continued until relapse. FL patients treated with R-MCP (n= 105) versus MCP (n= 96) had higher overall response (92 percent versus 75 percent, p= .0009) and CR rates (50 percent versus 25 percent, p= .0004), as well as improved progression-free survival (PFS; median not reached versus 29 months). Median overall survival (OS) was not reached for either group, but the four-year OS rates were significantly increased for R-MCP (87 percent) versus MCP (74 percent, p= .0096). Patients receiving R-MCP experienced more frequent grade 3-4 neutropenia, but without increased infectious episodes. To date, no patients have developed MDS or AML.
Overall Survival Time for 201 Follicular Lymphoma Patients Assigned to Chemotherapy With Either Mitoxantrone, Chlorambucil, and Prednisolone or MCP Plus Rituximab. Herold M, Haas A, Srock S, et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol 2007;25:1986-92. Figures reprinted with permission from the American Society of Clinical Oncology.
Overall Survival Time for 201 Follicular Lymphoma Patients Assigned to Chemotherapy With Either Mitoxantrone, Chlorambucil, and Prednisolone or MCP Plus Rituximab. Herold M, Haas A, Srock S, et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol 2007;25:1986-92. Figures reprinted with permission from the American Society of Clinical Oncology.
In Brief
For patients with advanced FL who require treatment, prospective phase III studies have shown improved outcomes for patients receiving rituximab plus chemotherapy as compared with chemotherapy alone, including R-CVP, R-CHOP, and, as shown in the present study, R-MCP. While CR, PFS, and OS are improved with these rituximab-containing regimens, none is curative, and the relative long-term benefit of incorporating doxorubicin or mitoxantrone up front remains uncertain. Potential adverse effects could include late cardiac or other toxicities and loss of some treatment options in the event of histologic transformation, although recent reports have suggested a decreased risk of transformation when an anthracycline is utilized with initial therapy. The ongoing PRIMA trial, comparing four different induction regimens — R-CVP, R-CHOP, R-FCM, and R-MCP — with post-induction randomization to maintenance rituximab versus observation, will be of considerable importance in addressing these treatment options. Correlative analyses of clinical, phenotypic, and molecular markers of response and resistance collectively and with each regimen will be of interest.
