Bendamustine Plus Rituximab Bests Current Standard of Care for Indolent Lymphoma

NEW ORLEANS, LA — Bendamustine (Treanda) plus rituximab (Rituxan; B/R) was superior to CHOP plus rituximab (CHOP-R) as first-line therapy of indolent lymphoma and mantle cell lymphoma in a multicenter, randomized, controlled trial of the German Study Group on Indolent Lymphoma (StiL). At an oral presentation at the 51^st ASH Annual Meeting, experts agreed that this study may be practice-changing.

“CHOP-R is standard therapy in most countries. This study showed that bendamustine/rituximab was much better tolerated than CHOP-R and, to our surprise, was clearly significantly superior in terms of progression-free survival [PFS],” said Mathias J. Rummel, MD, Head of the Department of Hematology, University Hospital in Giessen, Germany. “Bendamustine/rituximab has the potential to be the new standard of care for first-line treatment of indolent lymphoma,” Dr Rummel stated.

At present, there is no cure for indolent lymphoma. Patients included in the study were symptomatic, with a large tumor burden, splenomegaly, and pain. Dr Rummel said, “These patients clearly needed treatment.”

The study randomized 549 patients enrolled at 82 centers, with a median age of 64 to either B/R or CHOP-R. A total 513 patients were evaluable for toxicity and efficacy. Of these 513, 54% had follicular lymphoma, 13% had marginal zone lymphoma, 13% had mantle cell lymphoma (while not considered indolent, it was included because it is not curable with standard therapy), and 14% had other types of indolent lymphomas.

B/R caused significantly less hematologic toxicity than CHOP-R. The rates of grade 3-4 leukocytopenia were 12.1% in the B/R arm versus 38.2% in the CHOP-R arm (P <.001). Grade 3-4 neutropenia occurred in 10.7% of patients versus 46.5%, respectively (P <.001); and growth factor support with G-CSF was required by 4% of patients receiving B/R versus 20% taking CHOP-R (P <.0001). Alopecia did not occur in patients treated with bendamustine, whereas most patients treated with CHOP-R lost their hair, Dr Rummel said.A much smaller percentage of patients in the B/R arm than in the CHOP-R arm experienced paresthesias, stomatitis, skin reactions, infectious complications, and sepsis.

The overall response rate (ORR) was similar for the two regimens: 92.7% for B/R and 91% for CHOP-R. Complete responses occurred in more patients in the B/R arm (39.6% versus 30%, respectively). This translated to significantly better PFS: a median of 54.9 months for B/R versus 34.8 months for CHOP-R (P = .00012). Median follow-up in this study thus far is 34 months.

Bendamustine is used routinely in Europe as maintenance therapy for indolent lymphoma, but at a lower dose than the US license calls for, said Dr Rummel. The dose used in the study was 90 mg/m² for 2 consecutive days every 4 weeks. “The dose of bendamustine on the US label is much too high [120 mg/m² every 3 weeks]. I absolutely doubt that you can increase the efficacy of bendamustine by increasing the dose,” Dr Rummel commented.

In the US, bendamustine is approved for chronic lymphocytic leukemia and for indolent B-cell non-Hodgkin’s lymphoma that has progressed on rituximab or rituximab-containing therapy, and use as first-line therapy is off-label. Therefore, reimbursement can be challenging.“

Dr Rummel said that most patients with indolent lymphoma are maintained on rituximab. “In our study, there was no maintenance therapy, so we could evaluate the real difference between the two arms,” he said.

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ASH Abstract 405

Disclosures: Dr Rummel received honoraria and research funding from Roche Pharma AG and Mundipharma and honoraria from Amgen.