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Phase II Trial of CHOP Followed by Rituximab, a Chimeric Monoclonal Anti-CD20 Antibody, for Treatment of Newly Diagnosed Follicular Non-Hodgkin’s Lymphoma: SWOG 9800

Phase II Trial of CHOP Followed by Rituximab, a Chimeric Monoclonal Anti-CD20 Antibody, for Treatment of Newly Diagnosed Follicular Non-Hodgkin’s Lymphoma: SWOG 9800

The optimal therapy for advanced-stage follicular lymphoma is unknown. Combination chemotherapy usually induces remissions in most patients; however, nearly all patients eventually progress and there is no clear plateau on disease-free survival analysis. Single-agent treatment with the monoclonal anti-CD20 antibody rituximab (Rituxan) at 375 mg/m² weekly × 4 doses induces response rates of approximately 50% to 60% in patients with relapsed follicular non-Hodgkin’s lymphoma. In some patients, the molecular detection of disease by polymerase chain reaction assay may be eliminated following antibody therapy.

The Southwest Oncology Group (SWOG) investigated the safety and efficacy of adjuvant therapy with rituximab following conventional chemotherapy in 49 SWOG institutions. Patients were treated with six cycles of standard CHOP chemotherapy (cyclophosphamide [Cytoxan, Neosar] at 750 mg/m², doxorubicin HCl at 50 mg/m², vincristine [Oncovin] at 1.4 mg/m², and oral prednisone at 100 mg for 5 days), given at 3-week intervals. Patients with at least a partial (PR) or complete remission (CR) 4 weeks following the sixth cycle of CHOP were given four doses of rituximab at 375 mg/m² each week.

Objectives were to evaluate safety and determine 2-year failure-free survival and the rate of disappearance of clonal bcl-2 oncogene rearrangements from the peripheral blood and bone marrow following CHOP and rituximab. A total of 104 patients were registered to the study at closure on November 15, 1998, and 85 were determined eligible. The median age was 53 years (range: 27-76 years), 54% were male, and 10% had bulky stage II disease, 34% stage III, and 57% stage IV. Thirty percent had B symptoms and 31% had bulky disease.

Following CHOP chemotherapy, one patient died of infection. Grade 4 toxicities included 25 hematologic events, 1 cardiovascular, 1 gastrointestinal, and 1 unknown. There were 74 eligible patients registered to receive rituximab, and 73 were evaluable for toxicity. Following rituximab, 1 patient had grade 4 neutropenia and 12 patients had grade 3 toxicity.

A total of 84 patients have been evaluated for response following the combination of CHOP and rituximab. Fifty-four percent had a confirmed or unconfirmed CR and 18% a PR, for an overall response rate of 72%. Improvement in response following rituximab occurred in 16 patients (19%), with PR to CR in 14 patients, stable to CR in 1 patient, and unconfirmed CR to confirmed CR in 1 patient. Serial molecular monitoring of the t(14:18) translocation in the blood and bone marrow was performed and is being analyzed. The 2-year progression-free survival rate was 76% and the 2-year overall survival rate was 95%.

CONCLUSION: The addition of rituximab following conventional CHOP chemotherapy is well tolerated and provides additional antitumor activity. The prospective randomized ongoing trial SWOG 0016 is currently evaluating CHOP vs CHOP and combinations with rituximab or tositumomab/iodine-131 tositumomab (Bexxar) for the treatment of newly diagnosed advanced-stage follicular lymphoma.

Click here to read Dr. Bruce Cheson's commentary on this abstract.

 
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