Rituximab Improves Overall Survival in Previously Untreated CLL Patients

Adding rituximab to fludarabine and cyclophosphamide chemotherapy improves overall survival (OS) in patients with advanced, symptomatic chronic lymphocytic leukemia (CLL) compared with chemotherapy alone, according to a study by German researchers.

In a randomized study, 87.2% of patients with previously untreated CLL who received rituximab plus chemotherapy were alive after follow-up of more than 3 years compared with 82.5% who received chemotherapy alone, said Michael Hallek, MD, University of Cologne, Germany, lead investigator.

This marks the first time that an induction therapy has been shown to improve survival in a randomized trial in patients with advanced CLL, he said.

Rituximab binds to the CD20 antigen on the surface of normal and malignant B cells. It recruits the body's natural defenses to attack and kill the marked B cells. Stem cells (B-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B cells to regenerate after treatment and return to normal levels within several months.

"This is the first randomized trial to demonstrate that the choice of first-line therapy improves the natural course of CLL," said Hallek. "The results support the recommendation to use fludarabine, cyclophosphamide, and rituximab as standard therapy in physically fit patients with CLL."

He presented the second analysis of a study conducted in 191 study sites across 11 countries, in which 817 patients with untreated active CLL who were physically fit were randomized to treatment with either chemotherapy (fludarabine and cyclophosphamide) alone or rituximab plus chemotherapy, and followed for a median of 37.7 months.

The first analysis showed that patients receiving rituximab in combination with chemotherapy as first-line treatment lived an average of 40 months without cancer progression, compared with an average of 32 months for patients receiving chemotherapy alone.

The primary end point of the study was progression-free survival (PFS). Patients who received rituximab plus chemotherapy had a median PFS of 51.8 months, compared with 32.8 months for those who received chemotherapy alone. The median survival has not yet been reached.

At 3 years, PFS was achieved by 64.9% of patients in the rituximab/chemotherapy arm versus 44.7% of those in the chemotherapy alone arm.

OS was superior in the patients with Binet stage A or B who received rituximab, but not Binet stage C. Hallek explained that treatment intensity may not have been sufficient to demonstrate a significant survival benefit in Binet stage C patients because of their higher tumor load.

A complete response (CR) was observed in 44.1% of rituximab/chemotherapy recipients compared with 21.8% of patients receiving chemotherapy alone. Patients who achieved CR had better OS than those without CR.

Safety was consistent with previous studies of rituximab. The most common adverse events that occurred more often in the rituximab/chemotherapy arm included blood and lymphatic system disorders, infections, and neoplasms. Grade 3 or greater events that occurred more often in the rituximab/chemotherapy arm were hematologic toxicity, neutropenia, and leukocytopenia.