No Significant Improvement In the Outcome of Patients with Waldenström's Macroglobulinemia Treated Over the Last 25 Years
Authors: Kastritis Efstathios , Kyrtsonis Marie-Christine , Hadjiharissi Evdoxia , Symeonidis Argiris , Michalis Eurydiki , Repoussis Panagiotis , Tsatalas Konstantinos , Michael Michael , Sioni Anastasia , Kartasis Zafiris , Stefanoudaki Ekaterini , Voulgarelis Michael , Delimpasi Sosana , Gavriatopoulou Maria , Koulieris Efstathios , Gika Dimitra , Vervesou Elissavet , Konstantopoulos Konstantinos , Kokkini Garyfalia , Zomas Athanasios , Roussou Paraskevi , Anagnostopoulos Nikolaos , Economopoulos Theofanis , Terpos Evangelos , Zervas Konstantinos , Dimopoulos Meletios A. 
Published: October 2019

Abstract
Abstract 3032
The treatment of Waldenström's Macroglobulinemia (WM) has changed over the last decades, mainly since the introduction of nucleoside analogues and of rituximab in the management of this disease. Furthermore, novel agents such as bortezomib have been recently introduced. Several analyses in multiple myeloma indicated that the outcome of these patients has significantly improved over the last decade as a result of the introduction of novel agents. However, such data are not available for patients with WM. Thus, we performed an analysis in order to investigate whether the outcome of patients with WM has improved over the last years, compared to that of patients who started treatment before new drugs, such as rituximab became widely available, especially as part of the frontline treatment. We analyzed the database of the Greek Myeloma Study Group which includes 345 patients, who started treatment after January 1985: 130 patients initiated treatment before 1/1/2000 (Group A) and 215 patients started treatment after 1/1/2000 (Group B). More patients were males in both groups (54% in group A vs. 63% in group B, p=0.084), but patients in group B were older (median age 70 years vs. 65 years in group A, p=0.001). Patients in both groups started treatment mainly due to anemia (40% and 43% in groups A and B, respectively). Similar percentages of patients in groups A and B had hemoglobin ≤11.5 g/dl (74% vs. 77%, p=0.57), platelets ≤100,000/ml (12% vs. 14%, p=0.643), albumin ≤3.5 g/dl (44% vs. 50%, p=0.306) and elevated LDH (≥250 IU/L) (21% vs. 17%, p=0.422). The median serum M-peak levels were also similar (3.95 g/dl vs. 3.75 g/dl, p=0.485) while 5% and 7% of patients in groups A and B had a serum M-peak >7 g/dl (p=0.491). However, more patients in group B had serum beta2-microglobulin above 3 mg/dl (62% vs. 42%, p=0.004). Thus, according to the International Prognostic Scoring System (IPSS) for WM, 30%, 48%, and 22% had low, intermediate and high risk disease in group A and 15%, 42% and 43% in group B, respectively (p<0.001). Most patients (92%) who started treatment before 1/1/2000 were treated upfront with alkylating agent-based regimens without nucleoside analogues and only 4% of patients received frontline treatment with rituximab-based regimens. In contrast, in group B, most patients (78%) received rituximab-based regimens as initial treatment (p<0.001). A similar proportion of patients achieved at least partial response (63% in group A and 59% in group B, p=0.438) after initial treatment. The median overall survival (OS) for groups A and B was 106.5 and 94 months, respectively (p=0.327). In patients older than 70 years, the median OS in group A was 77 months and in group B was 62 months (p=0.982). There was no difference in the median OS in patients ≤70 years (120 vs. 121 months for groups A and B, respectively, p=0.897). When we evaluated cause specific survival, there was no difference in the outcome of patients who were older than 70 years and who started treatment before 1/1/2000 (median survival 98 months) compared to those who started treatment after 1/1/2000 (median survival 89 months, p=0.815). Similar data were obtained for cause specific survival of patients who were ≤70 years. There was no difference regarding OS or cause specific survival in each risk group of IPSSWM between patients who were treated before or after 1/1/2000. In order to adjust for differences in the baseline characteristics between patients of groups A and B, we performed a multivariate analysis using a Cox regression model. Again, we did not to find any significant difference between groups A and B for both OS (p=0.842) and cause specific survival (p=0.834). We conclude that our analysis of a large number of unselected patients with WM who initiated treatment over the last twenty five years, did not show any significant improvement in patients' survival, despite the fact that nucleoside analogues and rituximab were introduced in the management of this disease. This observation needs to be confirmed in other databases and may be explained by the indolent course of WM and by the lack of profound cytoreduction (i.e. low rate of complete response) in patients with high-risk disease. However, possible differences in the 15- or 20-year survival rate between the two groups may be detected with further follow-up of these patients.

Disclosures:
No relevant conflicts of interest to declare.