Bendamustine Active in Pts With Refractory B-Cell NHL

ATLANTA-The novel alkylating agent bendamustine appears to induce responses in patients with refractory B-cell non-Hodgkin's lymphoma (NHL), Jonathan W. Friedberg, MD, of the James P. Wilmont Cancer Center, Rochester, New York, said at the 47th Annual Meeting of the American Society of Hematology (abstract 229). The study was sponsored by Cephalon, Inc., which is developing the new agent as Treanda.

"Bendamustine is a multifunctional alkylating agent with novel mechanisms of action," Dr. Friedberg said. "It induces durable DNA damage in vitro, resulting in rapid cell death." The agent, which lacks cross-resistance with other DNA-targeting drugs, has previously shown activity in a variety of malignancies, including NHL, CLL, multiple myeloma, and breast cancer.

In a phase II multicenter study (SDX-105-01), Dr. Friedberg and his colleagues evaluated the efficacy of bendamustine monotherapy in patients with relapsed, indolent, or transformed rituximab (Rituxan)-refractory B-cell NHL. A total of 77 patients received 120 mg/m2 of bendamustine intravenously over 30 to 60 minutes on days 1 and 2 for up to six 21-day cycles. More than half of the patients enrolled (57%) had stage IV disease; 62% had follicular lymphoma, 16% had small lymphocytic lymphoma, and 18% had transformed NHL.

In a preliminary intent-to-treat analysis, bendamustine resulted in an overall response rate of 74%, including 35% achieving a complete response (CR) or unconfirmed CR and 39% a partial response (PR). An additional 7% maintained stable disease, while 16% had disease progression (responses in 4% were unknown). Objective responses were also noted in 60% of patients’ refractory to prior alkylators (20% CR/unconfirmed CR, 40% PR) with stable disease in 10%.

Median duration of responses in 57 evaluable patients was 7.8 months for patients with indolent disease vs 2.4 months for those with transformed disease for an overall median duration of 6.6 months.

"Bendamustine is well tolerated; the primary hematologic toxicity is reversible myelosuppression," Dr. Friedberg said. Almost half of patients (47%) developed grade 3-4 neutropenia (29% and 18%, respectively). Grade 3-4 leukopenia (41% and 9%) and thrombocytopenia (17% and 7%) were also common. Nonhematologic toxicities included nausea, fatigue, vomiting, fever, diarrhea, and constipation. Three grade 4 events were noted in one patient each: sepsis, pulmonary edema, and acute renal failure.

Dr. Friedberg concluded that "as a single agent, bendamustine shows high response rates in heavily pretreated NHL patients who are rituximab refractory and in patient's refractory to alkylator therapies." Given these preliminary results, investigators are currently enrolling patients in a pivotal phase III open-label, single-arm trial investigating the efficacy and safety of bendamustine in a similar patient population.

Take Away

Bendamustine, a novel alkylating agent, showed high response rates in heavily pretreated NHL patients refractory to rituximab or prior alkylators. A pivotal phase III trial is currently enrolling patients.