Old Drug Learns New Tricks for Lymphomas

A randomized, multicenter phase III clinical trial reported in The Lancet demonstrates that bendamustine plus rituximab (Rituxan; Genentech and Biogen IDEC) doubled progression-free survival (PFS) and increased the rate of 3-year PFS by 20% compared with the current standard-of-care combination of chemotherapy and rituximab (called R-CHOP) in first-line treatment for patients with indolent and mantle-cell lymphomas.

Cases of low white blood cell counts were reduced by more than a third, and, consequently, infectious complications also dropped, says Mathias Rummel, MD, PhD, head of hematology at the Hospital of the Justus-Liebig University Giessen in Giessen, Germany, and the study's principal investigator.

In addition, says Rummel, no patients will lose their hair with this new regimen. With R-CHOP (a combination of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) hair loss is common.

“This is the first study in a long time to show an improvement in the treatment of indolent and mantle-cell lymphomas in the first-line setting,” comments Caron Jacobson, MD, a hematologist at Dana-Farber Cancer Institute who was not involved in the study.

Bendamustine, a chemotherapy drug, has been used in Germany for decades, but it was considered experimental in the United States until 2008, when it was approved by the U.S. Food and Drug Administration for chronic lymphocytic lymphoma and advanced indolent lymphoma.

Whereas the more toxic R-CHOP regimen cures about 60% of cases among aggressive forms of non-Hodgkin lymphoma such as diffuse large B-cell lymphoma, no cure exists for the slower-progressing low-grade indolent and mantle-cell lymphomas.

“These patients have malignancies with long natural histories, so we're always looking for treatments to maximize efficacy and minimize toxicity,” says Jacobson.

Clinicians are already integrating this new first-line regimen into treatments for these diseases. Questions remain, however, about long-term use of bendamustine as well as maintenance after treatment with bendamustine plus rituximab.

Recent studies have shown that maintenance with rituximab after R-CHOP improves PFS rates. However, says Jacobson, “none of the trials has yet shown an improvement in overall survival. Given the long natural history of these diseases, these studies will require long follow-up to see a difference if one is there.”

In an ongoing phase II/III clinical trial, Rummel is comparing 2- and 4-year maintenance with rituximab after bendamustine plus rituximab. Because the trial does not include a group of patients without rituximab maintenance or a group that receives initial treatment with R-CHOP, says Jacobson, “it may not be possible to determine if rituximab maintenance improves outcomes with this new therapy the way it does with R-CHOP.”