Primary treatment of Waldenström macroglobulinemia with dexamethasone, rituximab, and cyclophosphamide.
OBJECTIVE
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).


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.


CONCLUSIONS
Our large, multicenter trial showed that the non-stem-cell toxic DRC regimen is an active, well-tolerated treatment for symptomatic patients with WM.
Dimopoulos
Meletios Athanasios
MA
Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece. meldimop@hotmail.com
Anagnostopoulos
Athanasios
A
Kyrtsonis
Marie-Christine
MC
Zervas
Konstantinos
K
Tsatalas
Constantinos
C
Kokkinis
Garyfallia
G
Repoussis
Panagiotis
P
Symeonidis
Argyris
A
Delimpasi
Souzana
S
Katodritou
Eirini
E
Vervessou
Elina
E
Michali
Evridiki
E
Pouli
Anastasia
A
Gika
Dimitra
D
Vassou
Amalia
A
Terpos
Evangelos
E
Anagnostopoulos
Nikolaos
N
Economopoulos
Theophanis
T
Pangalis
Gerasimos
G
D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab; D003907:Dexamethasone; D003520:Cyclophosphamide