Addition of Rituximab to Combination Chemotherapy Improves Response Rates in Mantle Cell and Other Lymphomas

Oncology NEWS International Vol 12 No 5, Volume 12, Issue 5

Tumor Board | <b>Julie M. Vose, MD, MBA</b>

This special supplement to Oncology News International includes updated results of studies with anti-CD20 therapy and other targeted therapies in the treatment of lymphomas, chronic lymphocytic leukemia, and immune thrombocytopenic purpura. The results were presented at the American Society of Hematology 44th Annual Meeting in Philadelphia, December 6 to 10, 2002.

MUNICH-The prognosis for patients with mantle cell lymphoma (MCL) remains poor despite investigations of multiple combination chemotherapy strategies.[1] The 5- year overall survival rate is 27% and less than 11% of patients are disease free at 5 years.[2] Because of the beneficial effects of rituximab (Rituxan) in non-Hodgkin's lymphoma[3] and its favorable tolerability profile when added to chemotherapy,[4] Wolfgang Hiddemann, MD, PhD, professor of internal medicine at Ludwig-Maximilians- University in Munich, and other members of the German Low Grade Lymphoma Study Group (GLSG) conducted two prospective, randomized trials of rituximab plus combination chemotherapy (ASH abstract 339).[5] In the first-line treatment trial, the GLSG compared cyclophosphamide (Cytoxan, Neosar), doxorubicin, vincristine (Oncovin), and prednisone (CHOP) vs rituximab plus CHOP (RCHOP) against follicular lymphoma, immunocytoma, and mantle cell lymphomas.[ 5] The 272 patients evaluable for response included 62 patients with MCL (see Table 1).[5] Treatment with R-CHOP resulted in a significantly (P = .019) greater overall response rate compared with CHOP treatment alone. Furthermore, the time to treatment failure was 435 days for the CHOP-alone treatment group, but was not reached in the R-CHOP treatment group.

Importantly, a subset analysis of the 62 patients with mantle cell lymphoma demonstrated a significantly greater overall response rate of 97% for patients treated with R-CHOP compared with 69% for patients treated with CHOP (P = .004). Relapsed, Refractory Disease As second-line therapy, patients with relapsed or refractory lymphoma, including follicular lymphoma, immunocytoma, and mantle cell lymphoma, were treated with fludarabine (Fludara), cyclophosphamide, and mitoxantrone (Novantrone), the FCM regimen, or with rituximab plus FCM (R-FCM). In this study, 94 patients were evaluable, including 35 patients with MCL. The overall response rates for both treatment groups were comparable (see Table 1).[5] Progression-free survival, however, was significantly longer in the R-FCM treatment group compared with the FCM treatment group (median, 483 days vs 213 days, P = .048). Collective Impact The results of these two studies suggest that the addition of rituximab to chemotherapy in both first-line and second-line treatment improves overall response rates and significantly improves progression-free survival in MCL compared with chemotherapy alone. Overall response rates with singleagent rituximab in MCL have ranged from approximately 20% to 46%,[6- 12] with median response duration as high as approximately 438 days. [11] Although the investigators did not study rituximab as single-agent therapy, the current studies do support further investigation of rituximab plus combination chemotherapy. Based on these results, rituximab plus chemotherapy may become a new standard for the treatment of MCL.


1. Bertoni F, Ghielmini M, Cavalli F, et al: Mantle cell lymphoma: new treatments targeted to the biology. Clin Lymphoma 3:90-96, 2002.
2. The Non-Hodgkin’s Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. Blood 89:3909-3918, 1997.
3. McLaughlin P, Grillo-Lopez AJ, Link BK, et al: Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 16:2825-2833, 1998.
4. Czuczman MS, Grillo-Lopez AJ, White CA, et al: Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol 17:268-276, 1999.
5. Hiddemann W, Unterhalt M, Dreyling M, et al: The addition of rituximab (R) to combination chemotherapy (CT) significantly improves the treatment of mantle cell lymphomas (MCL): results of two prospective randomized studies by the German Low Grade Lymphoma Study Group (GLSG) (abstract 339). Blood 100:92a, 2002.
6. Foran JM, Gupta RK, Cunningham D, et al: A UK multicentre phase II study of rituximab (chimaeric anti- CD20 monoclonal antibody) in patients with follicular lymphoma, with PCR monitoring of molecular response. Br J Haematol 109:81-88, 2000.
7. Nguyen DT, Amess JA, Doughty H, Hendry L, Diamond LW: IDECC2B8 anti-CD20 (rituximab) immunotherapy in patients with low-grade non-Hodgkin’s lymphoma and lymphoproliferative disorders: evaluation of response on 48 patients. Eur J Haematol 62:76-82, 1999.
8. Ghielmini M, Schmitz SF, Burki K, et al: The effect of rituximab on patients with follicular and mantlecell lymphoma. Swiss Group for Clinical Cancer Research (SAKK). Ann Oncol 11(Suppl 1):123-126, 2000.
9.Tobinai K: Clinical trials of a mouse-human chimeric anti-CD20 monoclonal antibody (rituximab) for B cell non-Hodgkin’s lymphoma in Japan. Cancer Chemother Pharmacol 48(Suppl 1):S85-S90, 2001.
10. Coiffier B, Haioun C, Ketterer N, et al: Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Blood 92:1927-1932, 1998.
11. Foran JM, Rohatiner AZS, Cunningham D, et al: European phase II study of rituximab (chimeric anti- CD20 monoclonal antibody) for patients with newly diagnosed mantlecell lymphoma and previously treated mantle-cell lymphoma, immunocytoma, and small B-cell lymphocytic lymphoma. J Clin Oncol 18:317-324, 2000.
12. Foran JM, Cunningham D, Coiffier B, et al: Treatment of mantlecell lymphoma with rituximab (chimeric monoclonal anti-CD20 antibody): analysis of factors associated with response. Ann Oncol 11(Suppl 1):117-121, 2000.