As reported in the Journal of Clinical Oncology by Buske et al, the European Consortium for Waldenström’s Macroglobulinemia (ECWM)-1 study has shown a numeric benefit in progression-free survival with the addition of bortezomib to dexamethasone, rituximab, and cyclophosphamide (DRC; B-DRC) in the first-line treatment of Waldenström’s macroglobulinemia.
Study Details
In the trial, 204 patients from sites in seven European countries were randomly assigned to receive B-DRC (n = 102) or DRC (n = 100). DRC was given as dexamethasone at 20 mg on day 1, rituximab at 375 mg/m2 intravenously on day 1 of cycle 1 and 1,400 mg subcutaneously on day 1 of cycles 2 to 6, and cyclophosphamide at 100 mg/m2 twice daily on days 1 to 5 for six cycles of 28 days. Bortezomib was given at 1.6 mg/m2 subcutaneously on days 1, 8, and 15 of each cycle. The primary endpoint was progression-free survival.
Key Findings
After a median follow-up of 27.5 months, estimated 24-month progression-free survival was 80.6% (95% confidence interval [CI] = 69.5%–88.0%) in the B-DRC group vs 72.8% (95% CI = 61.3%–81.3%) in the DRC group (P = .32). At the end of treatment, major response (at least partial response) was observed in 80.6% of patients in the B-DRC group vs 69.9% of the DRC group (P = .10), with complete response/very good partial response in 17.2% vs 9.6% (P = .14).
Median time to first response was 3.0 months (95% CI = 2.8–3.2 months) in the B-DRC group vs 5.5 months (95% CI = 2.9–5.8 months) in the DRC group. The shorter time to response resulted in a higher overall response rate (78.5% vs 65.0%, P = .05) and major response rate (57.0% vs 32.5%, P < .01) in the B-DRC group after three cycles of treatment.
At best response, major response rates were 85.3% in the B-DRC group vs 82.4% in the DRC group (P = .60), with complete response/very good partial response in 32.7% vs 20.9% (P = .07).
Grade ≥ 3 adverse events occurred in 49.5% of patients in the B-DRC group vs 49.0% of the DRC group. Serious adverse events occurred in 14.1% vs 27.1% of patients. Peripheral sensory neuropathy of any grade occurred in 18 patients (17.6%; grade 3 in 2 patients) vs 3 patients (3.0%; all grade 1 or 2).
The investigators concluded, “This large, randomized study illustrates that B-DRC is highly effective and well tolerated in Waldenström’s macroglobulinemia. The data demonstrate that fixed-duration immunochemotherapy remains an important pillar in the clinical management of Waldenström’s macroglobulinemia.”
Christian Buske, MD, of the Institute of Experimental Cancer Research, University Hospital of Ulm, Ulm, Germany, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the French Ministry of Health and Institut National du Cancer and by Janssen and Roche. For full disclosures of the study authors, visit ascopubs.org.
