Combination Therapy Effective for Previously Untreated Waldenström Macroglobulinemia

Last Updated: 2009-06-22 16:55:47 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - Combination chemotherapy with the proteasome inhibitor bortezomib, dexamethasone, and rituximab is effective in patients with symptomatic, untreated Waldenström macroglobulinemia (WM), according to a report in the June 8th Journal of Clinical Oncology.

Various combinations of bortezomib, dexamethasone, and rituximab (BDR) have been shown in preclinical studies to have additive and possibly synergistic effects in killing tumor cells in lymphoma and myeloma models, the authors explain.

Dr. Steven P. Treon from Dana-Farber Cancer Institute, Boston, and colleagues investigated the activity of BDR in 23 patients with symptomatic, untreated WM.

Median IgM levels declined in all patients, from 4830 mg/dL pretherapy to 1115 at best response, the authors report. Only 2 patients continued to have IgM levels of 3000 mg/dL or above after treatment, compared with 13 patients pretherapy.

Median percentage of bone marrow involvement decreased from 55% to 10% with therapy.

Three patients achieved complete responses, 2 achieved near complete responses, 3 achieved very good partial responses, 11 achieved partial responses, and 3 had minor responses, the researchers note, for an overall response rate of 96% and a major response rate of 83%.

"These rates compare favorably with those achieved by one of the agents alone, for which overall response and major response rates of 40% to 50% have been reported," the investigators write. "Importantly, no complete responses or near complete responses have been observed with either bortezomib or rituximab alone in the primary treatment setting."

Eighteen patients remain free of disease progression after a median follow-up of 22.8 months, the report indicates, and the estimated time to progression will exceed 30 months.

Peripheral neuropathy was the most common treatment-related toxicity, but most patients showed significant improvement within 6 months.

There was an unexpectedly high incidence of herpes zoster (4 of the first 7 patients), but subsequent routine use of herpes zoster prophylaxis with either valcyclovir or acyclovir proved effective in all but one patient (who did not fill her prescription for valcyclovir).

"The use of BDR offers a stem-cell sparing approach to the therapy of WM and may be a particularly suitable regimen for those patients in whom more rapid remissions are needed," the authors conclude.

However, based on the regimen"s toxicity, the authors recommend "exploration of alternative schedules for bortezomib administration that includes weekly dosing," and the study was terminated prematurely in favor of a successor study that used once-a-week bortezomib.

Source:

J Clin Oncol 2009.


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