Originally published as JCO Early Release 10.1200/JCO.2007.10.9926 on June 18 2007

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Primary Treatment of Waldenström Macroglobulinemia With Dexamethasone, Rituximab, and Cyclophosphamide

Meletios Athanasios Dimopoulos, Athanasios Anagnostopoulos, Marie-Christine Kyrtsonis, Konstantinos Zervas, Constantinos Tsatalas, Garyfallia Kokkinis, Panagiotis Repoussis, Argyris Symeonidis, Souzana Delimpasi, Eirini Katodritou, Elina Vervessou, Evridiki Michali, Anastasia Pouli, Dimitra Gika, Amalia Vassou, Evangelos Terpos, Nikolaos Anagnostopoulos, Theophanis Economopoulos, Gerasimos Pangalis

From the Departments of Clinical Therapeutics, Internal Medicine, and the Second Department of Propedeutic Medicine, University of Athens School of Medicine; Department of Hematology, Sismanoglion Hospital; Department of Hematology, Metaxa Hospital; Department of Hematology, Evangelismos Hospital; Department of Hematology, Erikos Dynan Hospital; Department of Hematology, Genimata General Hospital; Department of Hematology, General Airforce Hospital, Athens; Department of Hematology, Theagenion Cancer Center, Thessaloniki; Department of Hematology, University of Alexandroupolis; Department of Hematology, University of Patras; Department of Hematology, Agios Savvas Cancer Center; and the Department of Hematology, University of Ioannina, Greece

Address reprint requests to Meletios A. Dimopoulos, MD, Department of Clinical Therapeutics, Alexandra Hospital, 80 Vass Sofias, Athens 11528, Greece; e-mail: meldimop{at}hotmail.com

Purpose: Alkylating agents and the anti-CD20 monoclonal antibody rituximab are among appropriate choices for the primary treatment of symptomatic patients with Waldenström macroglobulinemia (WM), and they induce at least a partial response in 30% to 50% of patients. To improve these results, we designed a phase II study that included previously untreated symptomatic patients with WM who received a combination of dexamethasone, rituximab, and cyclophosphamide (DRC).

Patients and Methods: Seventy-two patients were treated with dexamethasone 20 mg intravenously followed by rituximab 375 mg/m² intravenously on day 1 and cyclophosphamide 100 mg/m² orally bid on days 1 to 5 (total dose, 1,000 mg/m²). This regimen was repeated every 21 days for 6 months. Patients' median age was 69 years and many had features of advanced disease such as anemia (57%), hypoalbuminemia (40%), and elevated serum beta₂-microglobulin (43%).

Results: On an intent-to-treat basis, 83% of patients (95% CI, 73% to 91%) achieved a response, including 7% complete, 67% partial, and 9% minor responses. The median time to response was 4.1 months. The 2-year progression-free survival rate for all patients was 67%; for patients who responded to DRC, it was 80%. The 2-year disease-specific survival rate was 90%. Treatment with DRC was well tolerated, with 9% of patients experiencing grade 3 or 4 neutropenia and approximately 20% of patients experiencing some form of toxicity related to rituximab.

Conclusion: Our large, multicenter trial showed that the non–stem-cell toxic DRC regimen is an active, well-tolerated treatment for symptomatic patients with WM.

published online ahead of print at www.jco.org on June 18, 2007.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

This article has been cited by other articles:

				M. A. Dimopoulos, E. Kastritis, S. Delimpassi, A. Zomas, M. C. Kyrtsonis, and K. Zervas The International Prognostic Scoring System for Waldenstrom's macroglobulinemia is applicable in patients treated with rituximab-based regimens Haematologica, September 1, 2008; 93(9): 1420 - 1422. [Full Text] [PDF]