SAN FRANCISCOInterim results of a phase III European study show that combining conventional chemotherapy with the monoclonal antibody rituximab(Drug information on rituximab) (Rituxan) improves survival rates over chemotherapy alone in elderly patients with aggressive lymphoma.
Bertrand Coiffier, MD, head of the Department of Hematology, Hospices Civils de Lyon, France, presented the results at the plenary session of the 42nd Annual Meeting of the American Society of Hematology. The study was conducted by the Groupe d’Etude des Lym-phomes de l’Adulte (GELA), a large oncology cooperative group of more than 130 institutions in France, Belgium, and Switzerland.
The researchers randomized 400 previously untreated elderly patients (60 years or older) with stage II to IV diffuse large B-cell lymphoma to receive either standard CHOP chemotherapy (cyclophosphamide, doxorubicin(Drug information on doxorubicin), vincristine and prednisone(Drug information on prednisone)) every 3 weeks for eight cycles, or CHOP plus rituximab (375 mg/m2) administered on day 1 of each CHOP cycle.
The interim analysis after 1 year of follow-up included 328 patients with a median age of 69. Thus far, Dr. Coiffier said, the combination therapy, or "R-CHOP," has yielded the following clinical outcomes:
12-month overall survival: 83% (R-CHOP) vs 68% (CHOP) (P < .01).
12-month disease-free survival: 69% (R-CHOP) vs 49% (CHOP) (P < .0005).
Complete remission: 76% (R-CHOP) vs 60% (CHOP) (P = .003).
"These results are compelling because standard chemotherapy has shown only a 30% to 40% cure rate in a disease that can be rapidly fatal," Dr. Coiffier said. "This is the first new drug combination in 20 years to show an improvement in overall survival in aggressive NHL."
Adverse prognostic parameters were equally distributed between both arms of the study: 63% of patients had stage IV disease, 65% had elevated LDH (lactate dehydrogenase), 26% had bone marrow involvement, 52% had more than one extranodal disease site, and 60% had an IPI (International Prognostic Index ) of 2 or 3. An independent panel reviewed 86% of cases, and diffuse large B-cell lymphoma histology was confirmed in 87%.
Approximately 10% of patients on R-CHOP experienced a grade 3-4 infusion-related event during the first infusion of rituximab. Beyond these first infusion events, the addition of rituximab to CHOP chemotherapy did not appear to cause a clinically significant increase in adverse events over those seen with CHOP chemotherapy alone, Dr. Coiffier said.
Grade 3-4 toxicity included fever (14 patients in the CHOP arm vs 9 in the R-CHOP arm); infection (52 vs 37); cardiac (20 vs 21); neurologic (21 vs 12); and lung (24 vs 16).
Sixty-two patients withdrew early: 23 due to treatment failure (18 with CHOP, 5 with R-CHOP); 30 due to adverse events (17 with CHOP, 13 with R-CHOP); and 9 for other reasons.
Mechanism of Action
Rituximab is a chimeric anti-CD20 monoclonal antibody that marks both normal and malignant B cells for destruction by the patient’s own immune system, via both antibody-dependent, cell-mediated cytotoxicity and complement-dependent cytotoxicity, Dr. Coiffier said. Because developing stem cells do not express CD20, they are not harmed by exposure to rituximab. The agent is FDA approved for the treatment of relapsed or refractory low-grade or follicular, CD-20 positive, B-cell NHL.
An ongoing multicenter randomized phase III Eastern Cooperative Oncology Group (ECOG) study of CHOP vs R-CHOP has enrolled more than 500 patients to date. "It is important that this study is completed to verify and extend the interim analysis findings of the GELA study in a US-based setting," he said.