Randomized Phase III trial: Maintenance therapy with the monoclonal chimeric antibody rituximab compared to observation in patients with CD20+ B-cell Non-Hodgkins lymphoma

Abstract Clinical and pharmacokinetic data suggest that the effect of rituximab could be improved by prolonged exposure to the drug. To test for this hypothesis we performed a prospective randomized trial of rituximab maintenance therapy in patients with CD20+ B-cell Non-Hodgkins-Lymphoma. After completion of standard treatment patients were randomized to either observation or maintenance therapy with rituximab (375 mg/m2) every 3 months for 2 years. Patients after first line therapy as well as relapse patients were included in the study. Patients with aggressive lymphoma were enrolled if they had achieved a complete response (CR) after initial treatment. Patients with aggressive lymphoma with residual tumor mass were examined with positrone emission tomography (PET) and qualified for randomization if PET showed no signs of tumor activity. Patients with indolent lymphoma qualified for the study if at least a partial response (PR) was achieved. So far 162 patients (pts) with CD20+ B-cell Non-Hodgkins-Lymphoma were enrolled in this trial. Histological subtypes included diffuse large cell lymphoma (69 pts), follicular lymphoma (41 pts), mantle cell lymphoma (18 pts), primary mediastinal lymphoma (15 pts), marginal zone lymphoma (9 pts), Burkitt’s lymphoma (3 pts), immunocytoma (2 pts), primary intestinal lymphoma (1 pt), hairy cell leukemia (1 pt), chronic lymphocytic leukemia (1 pt) and unclassified B-cell lymphoma (2 pts). No severe adverse events were observed during rituximab maintenance therapy. We conclude that rituximab maintenance therapy is feasable, safe and well tolerated in patients with CD20+ B-cell Non-Hodgkins-Lymphoma. Results including event free survival and overall survival for the observation group and for the maintenance therapy group will be presented.

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Rituximab maintenenance therapy in CD20+ B-cell non-Hodgkin lymphoma - Interim results of a multicenter prospective randomised phase II study

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17524 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17524-17524 ◽

Cited By ~ 1

Author(s):

M. Witzens-Harig ◽

M. Hensel ◽

J. W. Schmier ◽

K. Neben ◽

A. Benner ◽

...

Keyword(s):

Maintenance Therapy ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Aggressive Lymphoma ◽

Pharmacokinetic Data ◽

Hodgkins Lymphoma ◽

Rituximab Maintenance ◽

Mediastinal Lymphoma ◽

Non Hodgkins Lymphoma

17524 Background: Clinical and pharmacokinetic data suggest that the effect of rituximab could be improved by prolonged exposure to the drug. Methods: To test for this hypothesis we performed a prospective randomized trial of rituximab maintenance therapy in patients with CD20+ B-cell Non-Hodgkins-Lymphoma. After completion of standard treatment patients were randomized to either observation or maintenance therapy with rituximab (375 mg/m2) every 3 months for 2 years. Patients after first line therapy as well as relapse patients were included in the study. Patients with aggressive lymphoma were enrolled if they had achieved a complete response (CR) after initial treatment. Patients with aggressive lymphoma with residual tumor mass were examined with positrone emission tomography (PET) and qualified for randomization if PET showed no signs of tumor activity. Patients with indolent lymphoma qualified for the study if at least a partial response (PR) was achieved. Results: So far 124 patients (pts) with CD20+ B-cell Non-Hodgkins-Lymphoma were enrolled in this trial. Histological subtypes included diffuse large cell lymphoma (55 pts), follicular lymphoma (24 pts), mantle cell lymphoma (16 pts), primary mediastinal lymphoma (12 pts), marginal zone lymphoma (8 pt), Burkitt’s lymphoma (3 pt), immunocytoma (2 pt), primary intestinal lymphoma (1 pt), hairy cell leukemia (1 pt), chronic lymphocytic leukemia (1 pt) and unclassified B-cell lymphoma (1 pt). No severe adverse events were observed during rituximab maintenance therapy. Results from an interim analysis including event free survival and overall survival for the observation group and for the maintenance therapy group will be presented. Conclusions: We conclude that rituximab maintenance therapy is feasable, effective, safe and well tolerated in patients with CD20+ B-cell Non-Hodgkins-Lymphoma. No significant financial relationships to disclose.

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Rituximab Maintenenance Therapy in CD20+ B-Cell Non-Hodgkin-Lymphoma - First Interim Results of a Prospective Randomised Phase II Study.

Blood ◽

10.1182/blood.v106.11.2454.2454 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2454-2454

Author(s):

Mathias Witzens-Harig ◽

Manfred Hensel ◽

Kai Neben ◽

Axel Benner ◽

Johann W. Schmier ◽

...

Keyword(s):

Maintenance Therapy ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Aggressive Lymphoma ◽

Pharmacokinetic Data ◽

Hodgkins Lymphoma ◽

Rituximab Maintenance ◽

Mediastinal Lymphoma ◽

Non Hodgkins Lymphoma

Abstract Clinical and pharmacokinetic data suggest that the effect of rituximab could be improved by prolonged exposure to the drug. To test for this hypothesis we performed a prospective randomized trial of rituximab maintenance therapy in patients with CD20+ B-cell Non-Hodgkins-Lymphoma. After completion of standard treatment patients were randomized to either observation or maintenance therapy with rituximab (375 mg/m2) every 3 months for 2 years. Patients with aggressive lymphoma were enrolled if they had achieved a complete response (CR) after initial treatment. Patients with aggressive lymphoma with residual tumor mass were examined with positrone emission tomography (PET) and qualified for randomization if PET showed no signs of tumor activity. Patients with indolent lymphoma qualified for the study if at least a partial response (PR) was achieved. So far 87 patients (pts) with CD20+ B-cell Non-Hodgkins-Lymphoma were enrolled in this trial. Histological subtypes included diffuse large cell lymphoma (38 pts), follicular lymphoma (17 pts), mantle cell lymphoma (16 pts), primary mediastinal lymphoma (11 pts), marginal zone lymphoma (1 pt), Burkitt’s lymphoma (2 pt), primary intestinal lymphoma (1pt) and unclassified B-cell lymphoma (1 pt). No severe adverse events were observed during rituximab maintenance therapy. We conclude that rituximab maintenance therapy is feasable, safe and well tolerated in patients with CD20+ B-cell Non-Hodgkins-Lymphoma. First results from an interim analysis including event free survival and overall survival for the observation group and for the maintenance therapy group will be presented.

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Quality of Life in Patients with B-Cell Lymphoma during Maintenance Therapy with the Anti-CD20 Antibody Rituximab.

Blood ◽

10.1182/blood.v110.11.4471.4471 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4471-4471

Author(s):

Mathias Witzens-Harig ◽

Christiane Heiss ◽

Axel Benner ◽

Manfred Hensel ◽

Kai Neben ◽

...

Keyword(s):

Quality Of Life ◽

Maintenance Therapy ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Rank Test ◽

Hodgkins Lymphoma ◽

Rituximab Maintenance ◽

Non Hodgkins Lymphoma

Abstract The introduction of rituximab into the treatment of malignant lymphomas of the B-cell lineage has had a major impact on the management of these diseases. In diffuse large B-cell lymphomas (DLBCLs) and follicular lymphomas (FLs) several multicenter prospective randomized trials consistently demonstrated an improved outcome when rituximab was added to chemotherapy. In addition, prolonged exposure to rituximab as maintenance therapy has been benefical in patients with FL and mantle cell lymphoma (MCL). For patients, the effect of any prolonged antitumor therapy on the quality of life (QoL) is a very important question. However, so far the question whether rituximab maintenance therapy may impair QoL in patients with Non-Hodgkins-lymphoma remains unanswered. To investigate this subject, we have performed a prospective randomized trial of rituximab maintenance therapy (8 cycles rituximab 375 mg/m2 every 3 months) versus observation in patients with CD20+ B-cell Non-Hodgkins-Lymphoma in our institution. Between July 2002 and December 2005, 106 patients (pts) were included into the trial. QoL was assessed with the standardized questionnaires EORTC-QLQ-C30 and EuroQol-5D. After statistical analysis with the Wilcoxon signed-rank test, we found no significant differences of the QoL between the rituximab treatment group and the observation group. We conclude that rituximab maintenance therapy is safe and does not impair quality of life in this patient population.

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Rituximab Maintenenance Therapy Prolongs Event Free Survival in Patients with CD20+ B-Cell Non-Hodgkin-Lymphoma.

Blood ◽

10.1182/blood.v110.11.4472.4472 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4472-4472

Author(s):

Mathias Witzens-Harig ◽

Manfred Hensel ◽

Johann W. Schmier ◽

Kai Neben ◽

Axel Benner ◽

...

Keyword(s):

Maintenance Therapy ◽

B Cell ◽

Interim Analysis ◽

Cell Lymphoma ◽

Aggressive Lymphoma ◽

Event Free Survival ◽

Free Survival ◽

Hodgkins Lymphoma ◽

Rituximab Maintenance ◽

Non Hodgkins Lymphoma

Abstract Clinical and pharmacokinetic data suggest that the effect of rituximab could be improved by prolonged exposure to the drug. To test for this hypothesis we performed a prospective randomized trial of rituximab maintenance therapy in patients with CD20+ B-cell Non-Hodgkins-Lymphoma. After completion of standard treatment patients were randomized to either observation or maintenance therapy with rituximab (375 mg/m2) every 3 months for 2 years. Patients after first line therapy as well as relapse patients were included in the study. Patients with aggressive lymphoma were enrolled if they had achieved a complete response (CR) after initial treatment. Patients with aggressive lymphoma with residual tumor mass were examined with positrone emission tomography (PET) and qualified for randomization if PET showed no signs of tumor activity. Patients with indolent lymphoma qualified for the study if at least a partial response (PR) was achieved. After recruitment of 172 patients a planed interim analysis was performed. Complete data sets of 162 patients (pts) with CD20+ B-cell Non-Hodgkins-Lymphoma were evaluable for analysis. Histological subtypes included diffuse large cell lymphoma (69 pts), follicular lymphoma (41 pts), mantle cell lymphoma (18 pts), primary mediastinal lymphoma (15 pts), marginal zone lymphoma (9 pts), Burkitt’s lymphoma (3 pts), immunocytoma (2 pts), primary intestinal lymphoma (1 pt), hairy cell leukemia (1 pt), chronic lymphocytic leukemia (1 pt) and unclassified B-cell lymphoma (2 pts). The interim analysis showed that event free survival was significantly prolonged in the rituximab maintenance group compared to the observation group (p<0.05). However, no difference in overall survival between the two groups was observed so far. Two patients in the treatment group developed WHO grade III adverse events (1 leucopenia, 1 infection). Both pts recovered shortly after appropriate treatment. We conclude that rituximab maintenance therapy is feasable, safe and well tolerated in patients with CD20+ B-cell Non-Hodgkins-Lymphoma and may prolong event free survival in this patient population.

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