Primary Treatment of Waldenstrom's Macroglobulinemia with Dexamethasone, Rituximab and Cyclophosphamide (DRC): Long Term Follow-up Analysis of a Phase II Study.
Authors: Dimopoulos Meletios A. , Hadjiharissi Evdoxia , Kyrtsonis Marie-Christine , Symeonidis Argiris , Repoussis Panayiotis , Michalis Eurydiki , Delimpasi Sosana , Tsatalas Costas , Tsirigotis Panagiotis , Vassou Amalia , Vervessou Elina , Katodritou Eirini , Gavriatopoulou Maria , Anagnostopoulos Nikolaos , Gika Dimitra , Terpos Evangelos , Zervas Konstantinos 
Published: October 2019

Abstract 2887

Poster Board II-863

Between November 2002 and April 2006, 72 patients with Waldenstrom's Macroglobulinemia (WM) were enrolled into this multicenter trial of primary treatment with DRC which consisted of dexamethasone 20 mg IV followed by rituximab 375mg/m2 IV on day 1 and oral cyclophosphamide 100 mg/m2 bid on days 1 to 5 (total dose 1000 mg/m2). DRC courses were repeated every 21 days for six courses and then patients without progressive disease were observed without treatment. Patient characteristics, toxicity and response data have been reported previously (Dimopoulos et al, J Clin Oncol 2007; 25:3344): 83% of patients achieved a response including 7% complete, 67% partial and 9% minor responses. In June 2009 we updated this study (minimum follow-up >3 years) in order to assess time to progression, time to next treatment, type of second-line treatment and response to this, overall survival (OS) and cause-specific survival (CSS) in which deaths unrelated to WM or complications of treatment were censored. Second line treatment was administered to patients who experienced progressive disease and also met criteria for treatment requirement based on consensus recommendations (Kyle et al, Sem Oncol 2003; 30:116). As of June 2009, 42 patients fulfilled the criteria for progressive disease (Kimby et al, Clin Lymphoma Myeloma 2006; 6:380) but 14 patients have not yet required second line treatment. The median time to progression was 35 months (95% Confidence Interval: 22-48 months) and the median time to next treatment requirement was 51 months. Among several factors who were analyzed for their possible correlation with shorter time to progression, only lymphadenopathy was significant (p<0.01), while splenomegaly was of borderline significance (p=0.06). Among 28 patients who received second line treatment, 19 patients were retreated with either rituximab alone (n=7) with DRC (n=8) or with rituximab combined with other agents (n=4) and 16 patients (84%) achieved a minor response or better. The remaining 9 patients were treated with alkylating agents (n=3), with nucleoside analogues (n=3) with bortezomib (n=2) or with high dose therapy (n=1) and 6 patients achieved a minor response or better. So far 27 patients (38%) have died including 11 patients from unrelated causes (3 lung cancer, 1 bladder cancer, 1 melanoma, 1 gastric cancer, 1 pancreatic cancer, 2 congestive heart failure, 1 cerebral stroke and 1 pancreatitis). No patient developed myelodysplastic syndrome or secondary AML and one patient developed diffuse large B-cell lymphoma. The probability for 5-year OS and CSS is 59% and 74%, respectively. The International Prognostic Staging System (IPSS) is predictive for both OS and CSS. The probability for 5-year OS is 100%, 67% and 43% for patients with low-, intermediate- and high-risk WM according to IPSS (p<0.01). Furthermore, the probability for 5-year CSS is 100%, 81% and 62% for patients with IPSS low-, intermediate- and high-risk WM (p=0.05). We conclude that this long-term follow-up analysis of the original phase II study showed that the DRC regimen is associated with a significant median time to progression and that most patients who develop disease progression respond again to rituximab-based regimens. So far, this regimen has not been associated with development of secondary myelodysplasia. The DRC regimen represents an active and safe treatment choice for patients with symptomatic WM.

Disclosures:

No relevant conflicts of interest to declare.