Primary Treatment of Waldenstrom’s Macroglobulinemia (WM) with Dexamethasone, Rituximab and Cyclophosphamide.
Authors: Dimopoulos Meletios A. , Anagnostopoulos Athanasios , Kyrtsonis Marie Christine , Tsatalas Constantinos , Kokkini Garyfallia , Repoussis Panagiotis , Zomas Athanasios , Symeonidis Argiris , Michali Evridiki , Anagnostopoulos Nikolaos , Terpos Evangelos , Economopoulos Theophanis , Pangalis Gerasimos 
Published: April 2020

Abstract
Introduction: The three main choices for the primary treatment of WM are alkylating agents, nucleoside analogues and rituximab. There is evidence that combinations of nucleoside analogues and rituximab are highly effective. However, when such regimens are administered, there are concerns regarding myelosuppresion, immunosuppression and impact on stem cell collection. We designed a phase II study which included previously untreated WM patients (with clearly defined criteria for initiation of treatment) who were treated with a combination of dexamethasone, rituximab and cyclophosphamide (DRC).
Patients and methods: Patients with WM received primary treatment with dexamethasone 20mg i.v. followed by rituximab 375mg/m2 i.v. on day 1 and cyclophosphamide 100mg/m2 p.o. bid days 1–5 (total dose 1000mg/m2). This regimen was repeated every 21 days for 6 courses.
Results: Since July 2002, 70 patients have been enrolled in this multicenter study. As of July 2006, 60 patients have completed the scheduled courses of treatment. Patients characteristics include: median age of 71 years (range 33 to 89 years), 63% male, 28% B symptoms, 32% splenomegaly, 40% lymphadenopathy, 25% hyperviscosity syndrome, 62% hemoglobin &lt;10g/dL, 43% serum monoclonal protein ≥4gr/dL, 36% serum albumin &lt;3,5g/dL, 40% serum β2 microglobulin &gt;4mg/dL. On an intent to treat basis, 70% of patients achieved at least 50% reduction of serum monoclonal protein concentration, including 7% of patients who achieved immunofixation-negative complete response. Furthermore in 20% of patients &lt;50% reduction of monoclonal protein or disease stability was observed, whereas progressive disease during treatment was documented in only 10% of patients. The median time to response was 4 months (range 0,7 months to 14 months). With a median follow-up of 24 months, 60% of patients are progression-free. With the exception of one patient who died of interstitial pneumonia, the DRC regimen was well tolerated. 20% of patients developed grade 3–4 neutropenia. Severe opportunistic infections were not observed. Mild or moderate effects related to rituximab infusion such as fever, rigors and headache were seen in 20% of patients. In patients where stem cell collection was attempted, this procedure was successful in all
Conclusion: Our large, multicenter trial showed that the non-stem cell toxic DRC regimen is an active and well tolerated treatment for symptomatic patients with WM. With this treatment, disease control can occur in the majority of patients without the risks of myelosuppression and immunosuppression which may occur when nucleoside analogues are used. This regimen may be particularly useful when high-dose therapy is an option for patients with WM.