ALBERT

Beschreibung: 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

Beschreibung: We have recently shown that serum free light chain ratio (sFLCR) provides independent prognostic information in patients with newly diagnosed MM (Kyrtsonis et al, Br J Haematol, 137: 240–243, 2007). The aim of the present study was to extend our previous observations in a multicenter setting and to investigate the potential additive effect of sFLCR to the ISS system, in determining the prognosis of patients with MM. We analyzed 214 newly diagnosed MM patients (125 kappa-, 89 lambda-). Serum free light chain levels were measured in sera drawn at diagnosis, using a latex-enhanced immunoassay (The Binding Site, Birmingham, UK). Then, the sFLCR was calculated, accordingly as kappa/lambda or lambda/kappa, depending on the monoclonal light chain type of the patient. Based on our previous study “high” sFLCR was defined as ratios ≥3.57 and ≥45.09 for kappa- and lambda- MM respectively. The median age of the patients was 68 years (33–92), 51% were males, 28%, 30%, and 42% had Durie-Salmon stages I, II, and III, 14% creatinine 〉2 mg/dl, and 13% had Bence-Jones MM. ISS stage was 1, 2, or 3 in 33%, 33%, and 34% of the patients, 48% had CRP ≥4 mg/l, 18% elevated LDH, 31% hemoglobin

Beschreibung: Background: MACOP-B or even chemotherapy (CT) with consolidation high dose therapy with autologous stem cell support (HDT-ASCT) have been considered superior to CHOP in PMLBCL. However, in the absence of randomized trials, there is no established optimal treatment for these patients. The role of R-CHOP in PMLBCL, which usually affects young patients, has not been established. Aims: To evaluate the efficacy of R-CHOP±RT in PMLBCL and to compare this approach with CHOP±RT administered to historical controls. Patients and Methods: Between 1994 and 2006, 74 patients with PMLBCL were treated in 6 participating centers. R-CHOP displaced CHOP in the treatment of PMLBCL at a given timepoint in each center. Thus 31 consecutive patients who received R-CHOP, were compared with 43 consecutive historical controls, who had been treated with CHOP prior to that point. Results: The median age of the patients was 30 years (17–82), only 2 patients (3%) were older than 60 years, and 47/74 (64%) were females. All individual IPI parameters as well as B-symptoms were also balanced between the two groups, with the exception of performance status. The median follow-up of currently alive patients was 28 and 73 months for patients treated with R-CHOP±RT and CHOP±RT respectively, the complete response (CR/CRu) rate was 97% vs 67% (p=0.002), and the overall response rate was 100% vs 79%, respectively (p=0.007). All relapses after CHOP occurred within 22 months from diagnosis. The 3-year failure free survival (FFS) was 93±5% vs 53±8% for patients who received R-CHOP±RT vs CHOP±RT (p=0.0006). Within the subgroup of patients with L/LI risk IPI, the corresponding 3-year FFS rates were 95±5% vs 58±10% (p=0.007), while they were 90±9% vs 45±12% (p=0.03) among patients with HI/H risk IPI. The 3-year event free survival (EFS) for all patients was 90±5% vs 51±8% (p=0.001). The 3-year overall survival (OS) was 97±3% vs 67±7% (p=0.008), while the 3-year lymphoma specific survival (LSS) was 100% vs 67±7% (p=0.002). Conclusions: R-CHOP and RT provided impressive results with no cases of primary refractory disease, no lymphoma-related deaths and only 2 failures recorded so far after a median follow-up of 28 months among 31 patients. Patients treated with R-CHOP had significantly higher CR, FFS, EFS, OS, and LSS rates, when compared with CHOP-treated historical controls. Based on these results we continue to treat PMLBCL patients with R-CHOP and RT, avoiding more intensive strategies. Further studies are warranted to investigate whether RT is needed after R-CHOP, especially in the case of a negative post-chemotherapy PET-scan.

Beschreibung: Introduction: An ISSWM was recently proposed (Morel et al, ASH 2006), which was based on a large number of patients treated primarily with alkylating agents and /or nucleoside analogues. The ISSWM based on 5 adverse covariates wich defined 3 risk groups: low, intermediate and high risk with 5-years survival rates of 87%, 68% and 36% respectively. In our current analysis, we assessed the impact of this system in patients with WM who received primary treatment with rituximab-based regimens. Patients and methods: Ninety-three previously untreated, symptomatic patients who received treatment either with single agent rituximab (21 patients) or with the combination of dexamethasone, rituximab, and cyclophosphamide (72 patients) were classified according to the ISSWM, which is based on 5 adverse covariates: age〉 65 years, hemoglobin ≤11.5 g/dl, platelet count ≤ 100 x 109/L, β2- microglobulin 70g/L. Low risk is defined by the presence of ≤ 1 adverse characteristics except age, high risk by the presence of 〉2 adverse characteristics and intermediate risk by the presence of 2 adverse characteristics or age 〉65 years. Results: The disease features of the 93 patients were typical of symptomatic WM: age 〉 65 years in 63%, males 65%, B-symptoms in 22%, splenomegaly in 29%, lymphadenopathy in 34%. 15% of patients were rated as low risk, 65% as intermediate risk and 20% as high risk. Criteria for initiation of therapy included cytopenia, hyperviscosity, constitutional symptoms, organomegaly or IgM-related disorders. Overall, 62% of patients were alive at 6 years. Median survival was not reached for low and intermediate risk and was 38 months for high risk patients (p=0.006). There was a clear separation of the survival curves in the three groups. At the time of last follow-up the percentage of patients alive was 100%, 82% and 58% for patients classified as low, intermediate and high-risk group respectively. Conclusions: The recently proposed ISSWM is applicable in patients with WM who receive primary treatment with rituximab-based regimens and may serve as a basis to compare outcomes in different studies.

Beschreibung: Abstract 5019 A new method for the quantification of IgGκ, IgGλ, IgAκ and IgAλ individually and of deriving IgGκ/IgGλ and IgAκ/IgAλ ratios (HLCR) has been recently made available, allowing measurements of the monoclonal component alone as well as of the polyclonal, non-tumor immunoglobulins (Ig) in plasma cell dyscrasias. The purpose of the present study was to retrospectively determine HLCR and to investigate its contribution in a series of 98 multiple myeloma patients at presentation and in 38 of them, during their disease's course. There were 45 women and 53 men (median age 67 years). Disease stages were evenly distributed (36%, 30%, and 34% in ISS stage 1, 2, and 3 respectively). Paraprotein was IgG in 74 patients (50 IgGκ, 24 IgGλ) and IgA in 24 (12 IgAκ, 12 IgAλ) of them. Seventy-one symptomatic patients received conventional treatment while the other 27 were asymptomatic and were regularly followed only. Of the 38 patients also studied during disease course, 28 had IgG- and 10 IgA-MM; the median number of disease fluctuation events studied (remision-relapse) was 3 (range 2–9). Patients' median follow-up was 31 months. HLC analyses were performed on a Dade Behring BN™II nephelometer using polyclonal sheep antibodies (Hevylite™, Binding Site, UK) and HLCR was calculated with the involved Ig (either G or A) as numerator. HLC and HLCR values were then compared with disease parameters and survival. Statistical analysis was performed by standard methods. At patients' presentation, median monoclonal HLC IgG and IgA were 25 g/L and 32 g/L respectively while in patients with IgG-MM median IgG HLCR was 24.5 and IgA HLCR 60 in IgA-MM. HLCR was not correlated to b2-microglobulin, hypercalcemia, LDH or bone disease, FLCs or FLCR. It strongly correlated with time to treatment (p=0.0000093) and with a shorter overall survival (p=0.03) using as cut-0ff HLCR values in the upper tertile of symptomatic patients (〉56 for IgG and 〉228 for IgA). Of patients also studied during their disease course, 25 out of 38 patients responded at least partially (PR) to first line treatment and 9 to a subsequent one; 20 relapsed and then responded again. In most patients HLCR followed disease fluctuations. It normalized in 9 patients and was below normal in 1 patient that achieved a complete (CR) or stringent response (sCR). In some patients HLCR allowed a better evaluation of disease status. In 5 thought to be responding, ηLCR remained stable or increased and disease course confirmed the fragility of the believed response. Interestingly, more than 50% of patients that received VAD showed greater reduction of the polyclonal Ig than the tumor Ig during treatment and sometimes thereafter. In conclusion, we provide evidence that HLCR correlates with survival in MM and allows, in some patients, better disease monitoring. Disclosures: Mirbahai: Binding Site Group Ltd: Employment. Bradwell:Binding Site: Equity Ownership, Patents & Royalties. Harding:Binding Site Group Ltd: Employment.

Beschreibung: 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

Beschreibung: Background: Current treatments for Waldenström's macroglobulinemia (WM) are not curative, and a standard of care does not exist. MYD88 L265P, a mutation identified in patients (pts) with WM, signals through interleukin-1 receptor-associated kinase 1 and Bruton's tyrosine kinase (BTK), leading to the constitutive activation of the NF-κB pathway (Yang, 2013). Ibrutinib (ibr), an oral inhibitor of BTK, attenuates the interaction between MYD88 and BTK and blocks BTK-dependent downstream signaling, inducing apoptosis of WM cells (Treon, 2012). In a phase 2 trial of ibr in previously treated WM, durable responses were seen (overall response rate [ORR] of 90.5% and an estimated 24-month PFS of 69.1%; Treon, 2015) leading to FDA and EU approval of ibr in pts with WM. Single-agent ibr indicated favorable responses in pts with WM failing prior monoclonal antibody therapy (Treon, 2015). Here, we report on the efficacy and safety of single-agent ibr in pts with WM refractory to the last rituximab-containing therapy. Methods: Pts with centrally confirmed diagnosis of WM and symptomatic disease requiring treatment per 2nd International Workshop on WM criteria were enrolled in this open-label, international, multicenter, phase 3 substudy (PCYC-1127 Arm C). Other key inclusion criteria included disease refractory to the last rituximab-containing therapy defined as either relapse after 50% by end of Cycle 1 (Figure), with continued improvement over time. Any-grade adverse events (AEs) occurred in 29 pts (94%), and grade ≥3 AEs in 16 pts (52%). Most common any-grade AEs (〉15%) included diarrhea (39%); hypertension (23%); neutropenia and upper respiratory tract infections (URTIs; 19% each); pyrexia; thrombocytopenia; and increased tendency to bruise (16% each). Common grade ≥3 AEs included neutropenia (13%); anemia, diarrhea, hypertension, and thrombocytopenia (6% each). Overall, 16 pts (52%) developed infections (10% grade ≥3). Serious AEs occurred in 6 pts (19%). All patients remain alive at data cut, with no events of IgM flare, atrial fibrillation or major bleeding. Dose reductions occurred in 4 pts (13%), with no dose reductions for hematologic toxicity. Two pts discontinued ibr-1 pt due to early PD (MYD88 wild-type), and 1 pt discontinued after 8 days of treatment due to an AE of gastrointestinal AL amyloidosis. Overall, 29 pts (94%) continue on ibr therapy. Additional data will be provided. Conclusions: Single-agent ibr is highly active in this heavily pretreated rituximab-refractory WM population, with a high ORR. No new or unexpected AEs were observed, with a manageable safety profile consistent with previous studies of single-agent ibr. Table 1. Baseline characteristics N=31 Median age, years (range) Age ≥ 65 years, n (%) 67 (47-90) 17 (55) ECOG, n (%) 0-1 2 25 (81) 6 (19) IPSSWM, n (%) Low Intermediate High 7 (23) 11 (35) 13 (42) Median serum IgM, mg/dL (range) 3830 (740-10700) Median b2-microglobulin, mg/L (range) 3.6 (1.7-24) Median hemoglobin levels, g/dL (range) 10.3 (6.4-14.6) Median platelet count (109/L) (range) 218 (51-896) Median absolute neutrophil count (109/L) (range) 2.9 (0.7-15.4) Median number of prior therapies (range) 4 (1-8) Types of prior therapies, n (%) Rituximab Corticosteroids Alkylating agentVinca alkaloids Proteasome inhibitor Purine analog Anthracyclines Immunomodulating agent Nucleoside analog Other 31 (100) 25 (81) 25 (81) 14 (45) 14 (45) 13 (42) 8 (26) 2 (6) 2 (6) 4 (13) Prior autologous stem cell transplantation, n (%) 2 (6) Figure 1. Figure 1. Disclosures Dimopoulos: Genesis Pharma: Research Funding; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Onyx: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Trotman:Janssen: Research Funding. Macdonald:Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; Lundbeck Canada: Consultancy, Honoraria, Other: Travel Expenses; Roche: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding. Tam:Janssen: Consultancy, Honoraria, Research Funding. Tournilhac:Roche: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Mundipharma: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Janssen: Honoraria; GSK: Other: Travel Expenses, Research Funding; Amgen: Other: Travel Expenses, Research Funding. Ma:Abbvie: Research Funding; Xeme: Research Funding; Novartis: Research Funding; Idera: Consultancy, Honoraria; Genentech: Consultancy, Honoraria, Speakers Bureau; Giliead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Research Funding. Heffner:Amgen: Consultancy. Shustik:Amgen: Honoraria; Roche: Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy; Novartis: Consultancy. García-Sanz:Janssen: Honoraria, Other: Travel, Accommodations, Expenses; Takeda: Honoraria, Other: Travel, Accommodations, Expenses; Novartis: Research Funding. Fernández de Larrea:Celgene: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses. Castillo:Otsuka: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; Biogen IDEC: Consultancy; Millennium: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding. Kyrtsonis:Amgen: Research Funding; Lilly: Research Funding; Genesis: Honoraria; Millenium: Research Funding. Leblond:Janssen: Consultancy, Honoraria, Speakers Bureau; Mundipharma: Honoraria; Roche: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau. Symeonidis:Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Celgene: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Roche: Consultancy, Other: Travel, Accommodations, Expenses; Amgen: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Pfizer: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; MSD: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Gilead: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Takeda: Research Funding; Actellion: Research Funding; Proton-Pharma: Research Funding; Astellas: Other: Travel, Accommodations, Expenses, Research Funding; Teva: Other: Travel, Accommodations, Expenses, Research Funding; ApoPharma: Research Funding; Genzyme: Other: Travel, Accommodations, Expenses, Research Funding; Alexion: Other: Travel, Accommodations, Expenses, Research Funding; GenesisPharma: Consultancy; Glaxo: Consultancy. Singh:Pharmacyclics LLC, an AbbVie Company: Employment. Li:Pharmacyclics LLC, an AbbVie Company: Employment. Graef:AbbVie: Equity Ownership; Pharmacyclics LLC, an AbbVie Company: Employment, Membership on an entity's Board of Directors or advisory committees. Bilotti:Pharmacyclics LLC, an AbbVie Company: Employment. Treon:Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Onyx: Consultancy, Research Funding. Buske:Roche: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Celgene: Honoraria, Other: Travel, Accommodations, Expenses; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Gilead: Consultancy.

Beschreibung: Abstract 3036 The ISS introduced by Greipp et al (J Clin Oncol 2005) represents today the most widely used staging system for patients with multiple myeloma (MM) because it is based on two readily available variables: serum albumin and beta2-microglobulin. Serum beta2-microglobulin not only reflects myeloma tumor load but it is also increased in patients with renal dysfunction. Thus, there have been concerns that ISS-3 stage may include MM patients with renal impairment in whom elevated beta2-microglobulin does not reflect tumor burden but rather the degree of renal dysfunction. To address this issue, we assessed the impact of patients' renal function on the prognostic performance of ISS. Our analysis included data from 1516 patients with symptomatic MM that had been entered into the database of the Greek Myeloma Study Group. Renal function was assessed by the estimated GFR (eGFR), which was calculated using the modified MDRD formula (eGFR in mL/min/1.73 m2 = 186 × (Serum Creatinine)−1.154 × (Age)−0.203 × (0.742 if female) × (1.212 if African-American) and the degree of renal dysfunction was staged according to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) classification of chronic kidney disease (CKD) as follows: stage 1 eGFR ≥90 ml/min; stage 2 eGFR of 60–89 ml/min; stage 3 eGFR of 30–59 ml/min; stage 4 eGFR of 15–29 ml/min and stage 5 eGFR

Beschreibung: Introduction: Monoclonal Gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant plasma cell disorder occurring mainly in the elderly population. Its evolution, association with various diseases and behavior is an interesting study field in an attempt to understand its pathogenesis and disease course. Aim: To study the grade of coexistence of non-malignant and malignant diseases along with disease evolution and behavior in patients with MGUS, diagnosed in a single center. Patients and methods:We studied 138 MGUS-patients that were diagnosed in our center and then followed up to a median of 36 months (6months - 22 years). Median age was 66 years (27-92 years). 57% were of female sex. Monoclonal heavy chain was IgG in 76%, IgA in 14% and IgM in 10% of the patients while 63% presented k-chain clonality. Non-malignant and malignant preexisting diseases were documented at the time point of MGUS-Diagnosis. Patients with B-NHL expressing monoclonal Protein were not classified as MGUS since malignant B-Lymphocytes can be responsible for its production. Results: 10.9% of the patients presented solid tumors. The most common malignancy was Prostate-Cancer in 8.5% of the male patients followed by Thyroid-Cancer which was present in 2.2% of the whole patient group.Hematological malignancies were existent in 10.9% of the patients. 4.3% presented myeloproliferative neoplasms while myelodysplastic syndromes were represented in 5% of the patients.18.1% of the patients presented with diverse benign tumors, 8% had been diagnosed with Diabetes Mellitus while 32.6% presented cardiovascular disease, mainly hypertension (23.2%). Hyperlipidemia was present in 8.7%. Finally 18.1% of the patients presented non-malignant thyroid disease, mainly hypothyroidism (10.9%) which is increased compared to the general population.17 MGUS-Patients (12%) presented disease evolution. 3 Patients evolved directly to multiple myeloma while 3 more evolved initially to smoldering myeloma (SMM) before developing overt myeloma. 8 patients evolved to SMM without any further progression. 2 patients with IgM-MGUS presented Waldenström's maroglobulinemia in the follow up while one patient developed a B-NHL. We performed a statistical analysis, where only abnormal serum free light chain ratio (sFLCR) was found to have a prognostic impact on MGUS-progression (p=0.03).Within this group of evolving MGUS-patients two of them presented a very remarkable course. The first one was diagnosed with MGUS while she was in remission after Hodgkin's Lymphoma. She evolved then to SMM confirmed by bone marrow biopsy with more than 10% plasma cell infiltration by immunohistochemistry. After being stable for several months, monoclonal protein was no longer detectable and plasma cells in the bone marrow were normal without any treatment. The second patient was initially diagnosed with MGUS with a high sFLCR of 60. She then evolved to SMM with further sFLCR-increase up to 100 but remained without treatment according to the guidelines at that time. Four years later she developed anemia and the final diagnosis was B-NHL. Conclusion: In our study group MGUS was associated with numerous malignant and non-malignant disorders. Hypothyroidism was a common finding, increased compared to the general population. MGUS-evolution was also observed however disease course was unexpected in some patients showing the heterogeneity of the disease. sFLCR was confirmed as a prognostic factor. Further study is necessary to investigate any possible implication of the above findings in the disease pathogenesis and course. Disclosures Kyrtsonis: Genesis: Honoraria; Millenium: Research Funding; Lilly: Research Funding; Amgen: Research Funding.

Beschreibung: Waldenström's Macroglobulinemia (WM) is a low grade lymphoma with a prolonged course and a median survival exceeding 7 years. However, there are patients who die of WM early during the course of the disease while a significant proportion of WM patients can survive ≥10 years. The characteristics of these two groups of patients may differ and their identification may augment the choice of risk adapted treatment strategies. The aim of our study was to identify and characterize patients with short survival due to WM as well as those with survival exceeding 10 years, and to compare their characteristics in order to evaluate clinical factors associated with poor or with good outcomes, based on data from a large database with long follow up. The analysis included 492 patients that have been entered in the prospectively maintained database of the Greek Myeloma Study Group, who fulfill the criteria form symptomatic WM requiring therapy. The median follow up of all the patients in the database is 10 years. For the first part of the analysis we included 292 patients who have at least 10 years of follow up (thus, they started therapy at least 10 years ago, before 2006). Among them, we identified 101 (34.5%) patients who survived ≥10 years, and 13% who died due to WM within