Single-agent bendamustine has a high response rate in patients with advanced indolent non-Hodgkin’s lymphoma who had previously failed multiple courses of therapy, according to a presentation at the annual meeting of the American Society of Hematology.

The phase II study showed that 74 percent of patients responded to bendamustine, including 35 percent who achieved a complete response. All patients had disease that had progressed after previous therapy with rituximab, and a sizeable subgroup had also failed therapy with traditional alkylating agents.

Bendamustine is a novel hybrid cytotoxic alkylating agent that differs from conventional compounds in its apparent multi-functional mechanism of action. In addition to killing cells by damaging DNA and triggering apoptosis, bendamustine also causes mitotic catastrophe. Preclinical data suggest that the multi-functional mechanism of action may derive from the chemical structure, in which one molecular ring common to traditional alkylators is altered.

"It's unusual to see this kind of response in patients so far along in the course of the disease, especially since they previously did not respond to other alkylators and were relapsed from rituximab," commented principal investigator Jonathan W. Friedberg, M.D., Associate Director of Lymphoma Clinical Research at the University of Rochester Wilmot Cancer Center in Rochester, New York. "None of the available therapies for non-Hodgkin’s lymphoma are curative, so every patient will eventually require new therapeutic interventions. These data suggest bendamustine might prove to be such an alternative."

According to the study results, of objective responses in 74 percent of the 77 study participants, 35 percent had complete response; 39 percent partial response; 7 percent stable disease; and 16 percent had disease progression.

Among a subgroup of 28 patients whose condition was both refractory to rituximab and unresponsive to previous exposure to conventional alkylating agents, 64 percent responded to bendamustine. All assessments were based on standard International Working Group criteria.

Hematologic side effects were expected, manageable, and reversible. Grade 3 or 4 hematologic toxicities included leukopenia (50 percent), neutropenia (47 percent), thrombocytopenia (24 percent), anemia (9 percent), and febrile neutropenia (7 percent).

The most frequent non-hematologic adverse events were nausea (72 percent), fatigue (47 percent), vomiting (39 percent), fever (28 percent), diarrhea (25 percent), and constipation (24 percent). In addition, very low rates of hair loss were observed, occurring in only 5 percent of patients - and when observed it was mild (grade 1).

A Phase III trial of bendamustine in indolent non-Hodgkin’s lymphoma refractory to rituximab is ongoing at sites in the United States and Canada.