Long-term results from a multicenter Phase III study show that initial combination chemotherapy with bendamustine and rituximab more than doubled progression-free survival, to nearly six years, compared with standard R-CHOP therapy among patients with indolent (slow-growing) lymphoma and mantle cell lymphoma.

The bendamustine regimen was also associated with fewer side effects. The findings are expected to change clinical practice, especially in the U.S., where the R-CHOP regimen is still widely used.

"This is the first randomised clinical trial to compare bendamustine and rituximab with a standard chemotherapy regimen for these more challenging types of lymphoma, and it clearly shows that the bendamustine-based regimen is more effective and less toxic," said Mathias J. Rummel, MD, PhD, Professor of Medicine at the University Hospital Giessen in Germany and lead author of the study.

"Just as important, bendamustine-based therapy allowed patients to have a better quality of life while undergoing therapy. These long-term findings should be strong enough to change clinical practice."

R-CHOP, a standard chemotherapy regimen for many non-Hodgkin lymphomas, includes the targeted therapy rituximab plus the drugs cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine and prednisone.

Bendamustine has been used for decades in Europe (it was developed in Eastern Europe), but only became available in the U.S. in 2008. While many U.S. doctors already use the bendamustine-based regimen based on earlier data from this trial, uptake has not been universal. 

The investigators compared progression-free survival between 514 patients with previously untreated indolent non-Hodgkin or mantle cell lymphomas who were randomly assigned to receive either bendamustine/rituximab (B-R) or R-CHOP.

After a median follow-up of 45 months, median progression-free survival (PFS) was 69.5 months in the B-R group versus 31.2 months for the R-CHOP group. Overall survival did not differ between the two groups, partly because nearly half of the R-CHOP patients whose disease continued to progress were then permitted to receive B-R, and partly because survival for indolent lymphomas tends to be very long, making PFS the most reliable measure of clinical benefit and patient quality of life.

While there was a higher incidence of mild skin reactions in the B-R group, there was no hair loss and a lower incidence of nerve toxicity and infections, compared with the R-CHOP group. Moderate to severe declines in neutrophil counts (a type of white blood cell) occurred in 69 percent of the R-CHOP patients and 29 percent of the B-R group; G-CSF treatment (a drug used to boost neutrophil counts) was needed after 20 percent of R-CHOP chemotherapy cycles, but after only 4 percent of B-R cycles. 

Source: ASCO