ALBERT

Description: 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

Description: Abstract 3264 Life expectancy of thalassemic patients, appropriately transfused and adequately iron-chelated, has been substantially extended the last decades. However, these patients are subjected to particular risks which might favor the development of neoplasia, such as transfusional iron overload, high prevalence of viral diseases, particularly HCV infection, and transfusion-associated alteration of their immune status. The occurrence of neoplastic diseases has not been extensively investigated in this patient population. We sought to investigate the occurrence of neoplastic diseases during a 16.5 year-period, in a large cohort of 1972 thalassemic patients (homozygous beta-thalassemia N=1448, thalassemia intermedia N=352 and sickle-cell/beta thalassemia N=172), followed-up in 6 large Greek Thalassemic Units. All documented cases of neoplastic diseases, diagnosed during the period between 1.1.1996 and 30.6.2012 were collected and analyzed. The frequency of each type of neoplasia was then correlated with specific factors, potentially influencing the occurrence of these disorders, and particularly age at first transfusion, frequency of transfusions, previous splenectomy, smoking, use of hydroxyurea, previous autoimmune disorders, presence of HBV, HCV and HIV infection, adequacy of iron chelation and the degree of hepatic siderosis. Totally 38 cases of neoplastic disorders were documented among the 1972 patients. These were Hepatocellular carcinoma (10 cases), non-Hodgkin's Lymphoma (6 cases in total: Marginal-zone lymphoma N=2, Mantle-cell lymphoma N=1, Diffuse large B-cell lymphoma N=1, Burkitt's lymphoma N=1, T-cell lymphoblastic lymphoma N=1), Thyroid carcinoma (3 cases in total: papillary N=2, follicular N=1), Hodgkin's lymphoma (3 cases in total, classical N=2, LPHD N=1), Renal cell cancer (N=3), Colon cancer (N=3), Breast cancer (N=2), Cholangiocarcinoma (N=2), Pre-B Acute Lymphoblastic Leukemia (N=2), Testicular cancer (2 cases in total, seminoma N=1, teratoma N=1), melanoma (N=1), and Renal oncocytoma (N=1). Twenty-eight cases were diagnosed among patients with homozygous beta-thalassemia, 6 among patients with thalassemia intermedia and 4 among patients with sickle-cell/beta thalassemia. Median age at diagnosis of the neoplastic disease was 39 years (age range 21 to 63 years). Twenty-nine cases (76.3%) were diagnosed among previously splenectomized patients, although splenectomy had been performed in 41% of the total cohort of patients. All patients were HIV-negative, 3/31 (9.7%) were HBsAg-positive, whereas 22/37 (59.5%) had HCV infection. Patients were then classified according to the level of liver siderosis and the effectiveness of their iron chelation treatment, estimated by their annual median serum ferritin levels. Eleven patients were found to be adequately chelated (median serum ferritin 310 ng/ml), 16 were moderately-effectively chelated (median serum ferritin 1240 ng/ml) and 11 were inadequately chelated (median serum ferritin 2552 ng/ml). There was no difference in patient's age or in the type of neoplastic disorders occurred in each of the 3 categories, however 3/11 poorly chelated patients were long term survivors, versus 8/16 moderately chelated and 9/11 adequately chelated patients. In conclusion, the prolongation of overall survival of thalassemic patients results in increasing occurrence of neoplastic diseases among this patient population. Splenectomized and HCV-infected patients appear to represent higher-risk groups, whereas the role of iron overload appears not to influence the occurrence of neoplastic diseases but may have an impact on the long-term outcome and clearly deserves further investigation. Disclosures: No relevant conflicts of interest to declare.

Description: IgD multiple myeloma is a rare variant of the disease and in various series accounts for about 2% of patients with symptomatic myeloma. It has been suggested that patients with IgD myeloma may have an inferior outcome when compared to other patients. However, data on IgD myeloma patients treated in the novel agent era are lacking. In order to assess the frequency and evaluate the outcome and the specific characteristics of patients with IgD myeloma we analyzed the database of the Greek Myeloma Study Group to identify such patients. Between January 2000 and December 2012, among the 1239 patients with previously untreated, symptomatic, myeloma, 31 patients (2.5%) were diagnosed with IgD myeloma. Of interest, 84% of patients with IgD myeloma had lambda light chain (versus 38% of the patients with other subtypes of MM, p65 years (p=0.023) and 10% of patients with IgD versus 3.8% of the other patients were ≤40 years of age. Patients with IgD myeloma presented more often with significant renal dysfunction (serum creatinine ≥2 mg/dl in 52% versus in 19%, p

Description: Rituximab is a chimeric anti-CD20 monoclonal antibody, which targets both, autoreactive and neoplastic B-lymphocytes, thus representing a rational therapeutic approach for patients with various autoimmune disorders. However, although rituximab has been used asa treatment option for patients with autoimmune blood cytopenias, its optimal use has not yet been established. In an effort to analyze the effectiveness and safety of rituximab treatment in this patient population, we have retrospectively analyzed treatment outcome of 147 patients with various autoimmune blood cytopenias or related disorders (AutoImmuneHemolytic Anemia-AIHA N=31, Immune Thrombocytopenic Purpura-ITP N=67, Thrombotic Thrombocytopenic Purpura-TTP N=32, Evans’ Syndrome-ES N=10, Acquired Hemophilia-AH N=4, Anti-Phospholipid Syndrome-APS N=2 and Immune Neutropenia-IN N=1). Eligible patients should have received at least 3 courses of rituximab treatment, unless would have been died earlier due to treatment-related causes. Patients were 68 male and 79 female, with a median age of 52 years (range 15-87 years) and were treated following 1-7 (median 2) lines of previous treatment, for an early (12 months, N=39) or for refractory disease (N=48), at a median of 3.4 months following initial diagnosis (range 0.1-430 months). Eighteen patients received rituximab as first-line treatment due to contra-indication (N=10) or intolerance (N=8) of corticosteroids. Rituximab was administered at the classical dose of 375 mg/m2 (N=113) or at a reduced dose of 200 mg/m2 (N=26), whereas 8 patients initially received 375 mg/m2 for 1-6 cycles and continued with the reduced dose. Each patient received a median of 6 courses of rituximab (range 1-60 courses). Four out of 143 patients were HBsAg positive, and 62/133 were anti-HBc positive. These patients received lamivudineprophylaxis,throughout rituximab treatment and up to 6 months following rituximab withdrawal. Seven patients (4.8%) received

Description: Background: The EUMDS registry collects prospective observational data on lower-risk MDS patients from 142 centers in 17 countries. Red blood cell (RBC) transfusions remain one of the cornerstones in supportive care. Patients are prone to iron overload due to long-term iron accumulation either caused by RBC transfusions or ineffective erythropoiesis and associated iron toxicity through the formation of toxic iron species. Methods: We analyzed serum from 100 lower-risk MDS patients at six-month intervals for ferritin, transferrin saturation (TSAT), hepcidin-25, and toxic iron species (non-transferrin bound iron (NTBI) and labile plasma iron (LPI)) in order to evaluate temporal changes in iron metabolism and presence of potentially toxic forms of ironand their impact on survival. Results: Themedian age was 73 years (range 44-95 years). WHO2001 MDS-subtypes were RCMD (37%), RARS (30%), RA (18%), RAEB (7%), 5q-syndrome (4%) and RCMD-RS (4%). The table shows iron parameters at registration, 1 and 2 years follow-up both in transfusion-dependent (TD) and transfusion-independent (TI) patients and according to: MDS-RS (RARS/RCMD-RS) or MDS Other (RA/RCMD/RAEB/5q-syndrome). Serum ferritin levelswere increased in TD patients, compared to TI patients. Ferritin correlated significantly with hepcidin-25 (r=0.57, p80%) occurred almost exclusively in patients with MDS-RS and/or previous transfusions (Figure 1AC). Cox regression analysis for overall survival was adjusted for age at diagnosis, cumulative number of transfused units and TSAT, NTBI or LPI respectively as a time varying covariate. LPI showed a negative impact on overall survival (HR 1.97; 95%CI 0.39-9.92), independent of transfusion status (Figure 2), while NTBI and TSAT did not show relevant impact on overall survival (HR 1.04; 95% 0.91-1.20; HR 1.00; 95%CI 0.99-1.02, respectively). Conclusion: This is the first clinical outcome study which illustrates LPI as a clinically relevant assay format for identification of the toxic fraction of overt iron overload and its negative impact on overall survival. Table 1. Ferritin, Hepcidin-25, NTBI, LPI during follow-up Iron parameter Registration 1 yr follow-up 2 yrs follow-up N Median (p25-p75) N Median (p25-p75) N Median (p25-p75) Ferritin (µg/L)MDS Other: TI MDS Other: TD MDS-RS: TI MDS-RS: TD 94 51 13 26 4 274.0 (131.0 - 546.0) 188.0 (81.2 - 375.0) 408.0 (272.0 - 665.0) 271.5 (160.0 - 580.0) 947.5 (359.0 - 1333.5) 82 34 22 20 6 290.5 (149.0 - 845.0) 164.5 (78.3 - 293.0) 837.0 (550.0 - 1538.0) 257.0 (189.5 - 557.5) 1354.0 (859.0 - 2217.0) 64 28 15 11 10 346.5 (185.5 - 723.5) 204.5 (86.5 - 346.5) 642.0 (264.0 - 1970.0) 357.0 (222.0 - 597.0) 846.0 (590.0 - 1922.0) Hepcidin (nmol/L) MDS Other: TI MDS Other: TD MDS-RS: TI MDS-RS: TD 93 51 13 25 4 4.5 (2.7 - 8.4) 4.4 (2.7 - 8.3) 9.6 (4.5 - 26.3) 3.5 (1.5 - 4.9) 10.4 (7.9 - 13.5) 82 34 22 20 6 5.7 (2.7 - 12.7) 5.0 (2.3 - 8.1) 17.4 (10.2 - 23.7) 3.6 (1.7 - 5.0) 9.4 (8.8 - 14.4) 64 28 15 11 10 5.1 (2.5 - 8.9) 4.6 (2.5 - 7.1) 8.1 (2.4 - 12.8) 2.9 (1.3 - 6.1) 5.3 (2.9 - 9.3) NTBI (µmol/L) 0 RBC units 10 RBC units 91 78 12 1 0.65 (0.31 - 1.14) 0.58 (0.30 - 1.13) 0.94 (0.40 - 3.12) 0.81 (0.81 - 0.81) 76 52 12 12 0.57 (0.20 - 1.43) 0.53 (0.19 - 0.84) 0.58 (0.16 - 1.32) 2.97 (0.50 - 3.77) 60 39 14 7 0.62 (0.33 - 2.27) 0.52 (0.33 - 1.05) 1.64 (0.39 - 2.27) 3.31 (1.35 - 7.25) LPI (µmol/L) 0 RBC units 10 RBC units 91 78 12 1 0.13 (0.06 - 0.18) 0.13 (0.06 - 0.18) 0.13 (0.04 - 0.18) 0.13 (0.13 - 0.13) 76 52 12 12 0.12 (0.05 - 0.18) 0.11 (0.04 - 0.16) 0.07 (0.04 - 0.18) 0.20 (0.15 - 0.34) 60 39 14 7 0.10 (0.06 - 0.17) 0.10 (0.06 - 0.16) 0.11 (0.08 - 0.16) 0.18 (0.04 - 1.08) Figure 2. Impact of LPI on survival stratified by transfusion status (landmark analysis) Figure 2. Impact of LPI on survival stratified by transfusion status (landmark analysis) Disclosures de Witte: Novartis: Research Funding.

Description: 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

Description: 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.

Description: Background The outcome of lower-risk MDS patients with red blood cell transfusions (RBCT) dependency is inferior to that of RBCT independent patients, but whether the intensity of RBCT is important for prognosis is unknown. The EUMDS Registry is a non-interventional, observational longitudinal study enrolling patients with lower-risk MDS from 142 sites in 17 countries as described elsewhere (1). The EUMDS registry has accrued 1,902 patients as of July 21, 2015. We hypothesized that RBCT intensity is an independent prognostic factor for survival. Methods We first assessed the impact of RBCT intensity in the first year post-diagnosis (1yrPD) on progression-free survival among the 1034 patients who survived at least 1yrPD and had potential for a further year of follow-up. Secondly, we developed a longitudinal model of platelet counts throughout follow-up for 1660 patients in the registry with potential for at least one year follow-up. Results Among the 1034 patients, 323 patients had died: 67 after progression to higher-risk MDS/AML and 256 without progression. A further 41 surviving patients had progressed to AML. The overall 5-year survival was 52%. In a proportional hazards regression model (Table), the risk of death or progression increased in a non-linear fashion with age at diagnosis (p

Description: 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