ALBERT

Description: INTRODUCTION Anemia is the most frequent cytopenia in lower-risk MDS. Erythropoietic-stimulating agents (ESAs) are commonly used in these patients. The use of ÒclassicalÓ parameters (EPO and ferritin levels) and the revised IPSS (IPSS-R) has been proposed1 (SantiniÕs score) to predict response to ESAs and overall survival (OS) among patients with lower risk MDS by IPSS and a favorable Nordic group score2. OBJECTIVES The main objective of the study was to evaluate overall response rate (ORR) to ESAs and OS according to the proposed SantiniÕs score in an independent and large cohort of anemic lower risk MDS patients receiving treatment with ESAs. METHODS Data from 530 anemic patients with low/int1 risk IPSS de novo MDS (according to FAB and WHO criteria) and sufficient follow-up data available were recorded in Spresas3 (SPanish Registry of Erythropoietic Stimulating Agents Study from GESMD). Two hundred and twenty six patients (42.6% of the patients) were selected according to specific criteria regarding the published SantiniÕs score1: Hb level 350 ng/mL(=1) and IPSS-R very low=0, low=1, intermediate=2 and high=3) yielded a score ranging from 0 to 5. ESAs response rate and overall survival were analysed according to these score. Response to treatment was evaluated according to IWG 2006 response criteria and a multivariate logistic regression analysis was used to identify independent predictors of erythroid response (ER). OS were defined as the time between diagnosis and the corresponding event or last follow up (Feb 2015) and were analyzed using univariable and multivariable Cox proportional hazards regression methods. RESULTS Median age was 77 years (interquartile range [IQR] 25%-75%: 71-83 y), median Hb level at start of treatment was 10 g/dL (IQR25-75: 9-10), median EPO level was 90 (IQR25-75: 27,25-108) and median ferritin level was 338,5 (IQR25-75: 146,5-568,75). Among 139 patients with this data available, 85 patients (61,1%) were RBC transfusion dependent before ESAs treatment. Median time from diagnosis to ESAs treatment was 82 (IQR25-75: 27-353) days. According to the IPSS, 68.6% (N=155) and 31.4% (N=71) were in low and Int-1 risk groups, respectively. Regarding IPSS-R, 23% (N=52), 66.8% (N=151), 9.7% (N=22) and 0.4% (N=1) were in very low, low, intermediate and high risk, respectively. ORR to ESA treatment was 71.2% (N=161), with a median duration of response of 2.06 years. Prognosis factors of ER showed a trend toward to a higher ER among patients in the lower IPSS-R (P〉0.05), low IPSS (p=0.039) and lower EPO levels (p

Description: Chronic myelomonocytic Leukemia (CMML) is a heterogeneous clonal disorder highly resistant to the few therapies that are available nowadays. There is increasing evidence to suggest that Programmed Death-1 (PD-1), and its major ligand Programmed Death Ligand-1 (PD-L1), are involved in immune suppression and disease progression, are highly expressed in many hematological malignancies, and can be involved in MDS pathogenesis and resistance mechanisms to hypomethylating agents. However, the expression of PD-1 and PD-L1 is not widely explored in CMML. Different types of monocytes based on CD14 and CD16 expression show different genetic profiles and functions, having different distribution in several conditions, including malignancy. In our study, we studied the expression of PD-1 and PD-L1 in the peripheral blood (PB) monocytic compartment of patients with CMML using flow cytometry , to better understand their potential role in the pathogenesis of the disease, and as a basis for the evaluation of this pathway for the development of future immunotherapy strategies. Peripheral blood samples from 16 CMML, and age matched normal (n=10) and reactive (n=9) monocytosis (〉1 x109 /L) were studied. Two hundred µl of each PB sample were stained with an 8-color panel of monoclonal antibodies (CD16-FITC, CD64-PE, PD1-PCP5.5, PDL1-PC7, CD300-APC, CD14-APCH7, HLADR-V450 and CD45-OC515). A minimum of 1x 106 events were acquired by FACSCanto II (BD Biosciences, San Jose, USA) and the data was analyzed with the Infinicyt software (Cytognos SL, Spain). Monocytic population was selected first on the automated population separator plot and confirmed by the expression of CD64 and HLADR expression. Lymphocytes were used as the internal control. Three types of monocytes were defined based on the CD14 and CD16 expression, as previously described. As expected, CMML type 1 patients had higher absolute monocyte counts in PB than reactive and normal cases (p=0.001), and higher percentage of monocytic cells by flow (0.001). The distribution (median) of the monocytic subpopulations based on CD14 and CD16 expression among the monocytic compartment in PB of CMML, reactive and normal cases, respectively, was as follows: "classical"(CD14+CD16-) were of 98%, 90% and 85% (p

Description: Abstract 4051 Multiparameter flow cytometry (MFC) immunophenotyping has shown to be of value for differential diagnosis and minimal residual disease assessment in multiple myeloma. However, the clinical value of MFC immunophenotyping in other plasma cell disorders (PCD) remains largely unexplored. Systemic light chain (AL) amyloidosis is a rare PCD characterized by the accumulation of monoclonal light chain fragments leading to end-organ damage and short survival. Bone marrow (BM) plasma cell (PC) infiltration in AL is usually low and thus the identification of clonal PC can be often difficult by immunohistochemistry and/or immunofluorescence. In the present study we focused on 34 BM samples sent to our institution with a suspected diagnosis of AL. MFC immunophenotypic studies were performed using the following 4-color combinations of MoAbs (FITC/PE/PerCP-Cy5.5/APC): CD38/CD56/CD19/CD45 (n=34); in addition cy-Kappa/cy-Lambda/CD19/CD38 staining was add to confirm the clonal or polyclonal nature of BMPC in equivocal cases. Ploidy and cell cycle analysis were additionally performed in a subset of cases (n=12/34). From the total 34 cases included in the present study, 28 had a confirmed diagnosis of AL. The remaining 6 cases were finally diagnosed with localized - amyloidoma - (n=2) and familial (n=1) forms of amyloidosis, multiple myeloma-associated amyloid (n=2) and congestive pericarditis (n=1). Interestingly, the presence of clonal PC was detected by MFC in 27 of the 28 (96%) patients with AL; in turn, clonal PC were undetectable in the BM of all cases with localized and familial forms of amyloidosis. The median overall level of PC (M-PC plus N-PC) seen in MFC immunophenotypic analyses of BM samples of the 28 patients with AL was 1.9% (range: 0.1% - 15%), with a significant positive correlation between PC enumerated by MFC and conventional morphology (r=0.5; p=.01). Within the BMPC compartment, the median proportion of clonal PC was of 94% (mean 81% ± 29%); in 6 cases all BMPC were clonal while in the remaining 22 patients residual normal PC persisted (median of normal PC/BMPC 13% ± 31%). The most common aberrant phenotypes were down-regulation of CD19 (92%) and CD45 (83%), followed by overexpression of CD56 (56%) and infra-expression of CD38 (42%). Aneuploidy was only found in 18% of cases, all of them hyperdiploid. Cell cycle analysis showed a median % of S-phase and G2-Mitosis PC of 0.7% and 3.5%, respectively. Concerning patients' outcome, cases with undetectable normal PC (6/28, 21%) had a significantly decreased overall survival (OS) compared to patients with persistent BM normal PC at diagnosis (22/28, 79%) with 3-year OS rates of 0% vs. 59%, respectively (p=.001). In summary, these preliminary data suggests that MFC immunophenotyping investigations may be clinically relevant in patients with suspected amyloidosis for i) differential diagnosis between AL and other forms of amyloidosis and, ii) prognostication of patients with AL according to the presence or absence of baseline persistent normal PC. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction Temsirolimus (TEM) is an mTOR inhibitor EMA approved for the treatment of patients (pts) with relapsed or refractory (R/R) mantle cell lymphoma (MCL). In a phase III trial TEM 175mg weekly for 3 weeks followed by 75mg weekly significantly improved PFS (4.8 months)  and objective response rate (22%) compared with investigator’s choice (1.8 months, 2% respectively). TEM has also been tested in combination with rituximab (RTX) in a phase II trial with encouraging efficacy results (ORR 59%, median time to progression 9.7 months) even in rituximab-refractory pts. However, few data have been reported on the use of TEM in everyday clinical practice. Methods Sixteen Spanish centres participated in this retrospective, observational and multicenter study: Inclusion criteria were as follows: pts ≥18 at the time of treatment, confirmed diagnosis of R/R MCL treated with TEM between January 1st 2010 and  December 31st 2012. Endpoints were overall response (ORR), partial response (PR) and complete response (CR) rate, toxicity as CTCAE v3.0 of NCI scale and overall survival (OS) and progression free survival (PFS).This study was approved by the Ethic Committee of all participant sites (PFI-TEM-2010-01). Results A total of 24 patients were included, 15 pts treated with TEM in monotherapy (TEM 175mg weekly for 3 weeks followed by 75mg weekly) and 9 in combination with RTX (TEM 25mg/week plus RTX 375mg/m2 per week during the first cycle and a single dose of RTX every other 28-day cycle). 22 were male and the median age was 71 (range 53 to 84). Regarding histology grade, 17 (74%) pts had classic, 1 (4.3%) blastoid and 5 (21.7%) unknown. According to simplified MIPI prognostic score, 6 (26.1%) pts had low risk, 10 (43.5%) intermediate risk and 7 (30.4%) high risk. Five pts had 10-40% of Ki 67 index, 3 had 〉40% and 14 pts unknown. Median number of prior therapies in TEM monotherapy cohort was 2 (range 1 to 7) and 4 (range 2 to 8) in the combination cohort. Median duration of therapy was 3.07 months in the TEM monotherapy cohort and 2.03 months in the combination cohort. The overall response rate (ORR) with TEM in monotherapy was 60% (40% CR and 20% PR) and 6.7% of disease stabilization. For those patients treated with TEM plus RTX, the ORR was 78% (56% CR and 22% PR) and 20% of disease stabilization. Median PFS for patients who reached CR in TEM monotherapy cohort was 12.73 months (95%CI, 1.28 to 24.19) and 10.93 months (95%CI, 1.40 to 20.46) in the combination cohort. Overall the median PFS for all patients was 7.30 months (95%CI, 2.36 to 12.24). Two pts underwent allogeneic stem cell transplantation after successful TEM monotherapy treatment. In terms of tolerability, 13 pts of 15 developed at least one adverse event (AE) in the TEM monotherapy cohort and 5 pts of 9 in the combination cohort. Most common AE (all grades) were thrombocitopenia (75%) in both cohorts, rash (37%), diarrhea (12%), hyperglucemia  (12%), hyperlipemia (8%), mucositis (8%) and neumonitis (8%). Most common G3/4 adverse event was thrombocytopenia (33%). Conclusions Although this is a small sample size, TEM efficacy in this study seems to be higher compared to previous Phase II and III trials with an acceptable toxicity profile in pts with MCL. The median PFS in the combination therapy cohort was surprisingly lower than in the monotherapy cohort which may be explained by differences in clinical features between both groups. Disclosures: Off Label Use: Use of temsirolimus in combination with rituximab. Morán:Pfizer: Employment. Viqueira:Pfizer: Employment.

Description: In AL, a small PC clone synthesizes a misfolded light-chain that forms amyloid fibrils causing organ dysfunction. Significant progress was made regarding the characterization of the amyloid fibrils, but little attention has been paid to the molecular features of clonal PCs; this is most likely explained by the low tumor burden in AL, often masked by a polyclonal PC background. Here, we investigated the phenotypic, transcriptomic and genomic profile of clonal PCs from a total of 22 patients with newly-diagnosed AL. Through multidimensional (12-color) flow cytometry (MFC) combining the evaluation of 10 antigens plus cyκ/cyλ (thus confirming clonality of aberrant phenotypes), we detected clonal PC in all 22 (100%) patients (median 0.76%; range: 0.01% - 30%). Clonal PCs mainly differed from normal PCs by down-regulation of CD19 (100% of cases), CD27 (50%), CD38 (41%), CD45 (50%) and CD81 (50%); CD117, CD28 and CD56 were aberrantly bright positive in 32%, 50% and 64% of patients, respectively. Principal component analysis showed overlapping immunophenotypic expression profiles between clonal PC from AL vs multiple myeloma (MM) and MGUS patients. Using patient-specific aberrant phenotypes, we then sorted clonal PCs (purity ≥97%) by MFC for subsequent molecular studies. Gene expression profiling (GEP) was performed (HumanGene1.0ST) on extracted RNA from clonal PCs of 10 of the 22 AL patients, and compared to FACS-purified PCs from 7 healthy donors. Overall, clonal PCs showed deregulation (SAM Excel add-in with a FDR q-value25 consecutive imbalanced markers per segment, 〉100Kb length and

Description: Background: Eltrombopag is a thrombopoietin receptor agonist approved for primary chronic ITP patients. Due to the non-existence of clinical trials using eltrombopag in persistent and newly diagnosed ITP, there are no clear data about its usefulness in this setting. Aims: To evaluate efficacy and safety of eltrombopag in persistent, newly diagnosed and chronic ITP in routine clinical practice in Spain. Methods: Two hundred and twenty adult ITP patients from thirty Spanish centers who had been treated with eltrombopag and included in the Spanish Eltrombopag Registry were retrospectively evaluated. This study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: Here we report efficacy and safety results of primary ITP Spanish Eltrombopag Registry cohort. According to the standard definition, patients were allocated to newly diagnosed (n=30), persistent (n=30) and chronic (n=160) ITP groups. Each group is described separately in Table I. There are no statistical significant differences regarding response and duration of response among ITP groups. There is a trend towards a greater efficacy in newly diagnosed ITP with 93.3% of responses (platelet count ≥30 x109/L and at least two-fold increase the baseline count and absence of bleeding) and 86.7% of complete responses (CR; platelet count 〉100 x 109/L). Persistent ITP achieved 83.3% of responses and 80.0% of CR. Similarly 79.4% of responses with 73.1 of CR were observed in chronic ITP. Response rates were similar in all groups regardless all other studied parameters. Another trend towards a longer response duration in persistent ITP was found, with a median of 424 (IQR, 288-664) days. Response durations were similar in chronic ITP (median, 370 days; IQR, 174-624) and in newly diagnosed ITP (median, 378 days; IQR, 154-485). In newly diagnosed ITP, eight adverse events (AEs) with only three grade 3-4 AEs were observed. We reported three deaths; Two of them were due to upper respiratory tract infections in previously diagnosed pulmonary patients. A cerebral hemorrhage was the only death directly related to thrombocytopenia. In persistent ITP, four grade 1-2 AEs and two grade 3-4 AEs (one stroke, one cerebral bleeding) were reported. The only observed death was secondary to the mentioned cerebral hemorrhage. Twenty-one grade 1-2 AEs, ten grade 3-4 AEs and eight deaths (only two caused by bleeding) occurred in chronic ITP. Conclusion: Use of eltrombopag for treating persistent and newly diagnosed ITP is effective and safe. However, more studies are needed to confirm usefulness of TPO-RAs in this setting. Table 1. Patient characteristics Variable Newly-Diagnosed ITP (n = 30) Persistent ITP(n=30) Chronic ITP (n=160) Age, years, median [Q1;Q3] 66[46;79] 66[47;76] 61[47;75] Men/Women n 12/18 15/15 47/113 Charlson comorbidity Index 〉 1, n (%) 7(25.9) 5(17.2) 25(16.7) Months with ITP, median [Q1;Q3] 1[1;2] 6[4;10] 79[30;193] Past ITP treatments, median [Q1;Q3] Rituximab, n (%) Splenectomy, n (%) Romiplostim, n (%) 2[1;3] 3(10.7) 2(7.1) 3(10.7) 2[1;3] 5(17.2) 4(13.8) 4(13.8) 3[2;4] 43(28.3) 47(30.7) 37(24.3) Platelet count at start of eltrombopag treatment, (x109/L), median [Q1;Q3]Bleeding at start of eltrombopag treatment , n (%)Concomitant treatment, n (%) Corticoids Immunoglobulins Corticoids and Immunoglobulins 15[7;29] 13(43.3) 10(33.3) 6(60) 0 2(20) 14[6;26] 10(33.3) 9(30) 7(77.8) 0 2(22.2) 22 [9;38] 50 (31.3) 46 (28.8) 27 (57.4) 10 (21.3) 8 (17) Disclosures Off Label Use: We describe the possibility of using eltrombopag, an oral thrombopoietin receptor analog, for persistent and newly diagnosed ITP patients..

Description: Background and Objectives: B-cell chronic lymphoid leukemia (CLL) is a lymphoproliferative disorder where specific microenvironment between B-cells and nurse-like Cells (NLC) seem to be involved in disease progression providing cell survival, proliferation and drug resistance. Consequently, functional screening platforms that can assess drug candidates within this microenvironment are needed. Our aim is to show the ability of the Exvitech® automated flow cytometry platform to screen agents that interfere with the microenvironmentxs protective scenario such as ibrutinib or idelalisib or standard CLL drugs such as fludarabine or prednisolone. This approach will allow us to select candidates in an in vitro assay and could personalize the treatment according the response to the drugs. Patients and methods: We have adapted Jan Burger's published assay1. Peripheral blood mononuclear cells (PBMCs) from not previously treated CLL patients were isolated by density gradient centrifugation over Ficoll-Pacque and were used fresh (N=14) or cryopreserved (N=6). B-cells were assessed to be 〉90% viable by flow cytometry. NLC co-cultures were stablished by suspending PBMCs from CLL patients in complete RPMI medium with 10% FBS to a concentration of 2x107/ml. Cells were incubated for 14 days in 96-well plates and presence of NLC was confirmed by microscopy. After that, viability was investigated in B-cells treated with 8 concentrations of ibrutinib, idelalisib, fludarabine and prednisolone after 72h of incubation with annexin-V and the appropriate CLL flow cytometry markers. Drug response was evaluated as a depletion survival index of the B-cell population relative to the average of the control wells with NLC but without drug. Results: As expected, depletion of B-cells cultured without NLCs were significant greater than with NLC after the 72h incubation supporting the assay where NLCs protect B-CLL cells from in vitro spontaneous apoptosis. In a similar way, viability of fresh samples with NLC was higher than the corresponding frozen samples (84% vs 25%), though both could be used. Our results show a lower pharmacological median potency, measured as a higher EC50, when we work with NLC versus without NLC for ibrutinib (10µM vs 4µM), idelalisib (17µM vs 0.4µM) and prednisolone (3.5µM vs 1.5µM). However, the effect of fludarabine seems to be independent of the presence of the NLC in the cell culture (7µM vs 6µM). This is consistent with the protective role of microenvironment; more pronounced for ibrutinib and idelalisib. Interestingly with NLC, for each drug there is a significant interpatient variability (Figure 1); each line correspond to a different patient, reflecting the possibility that patients might be more sensitive or resistant to a certain drug in this particular scenario. There is a higher degree of patient sample stratification for idelalisib, fludarabine or prednisolone, where there are still an important % of B-cells alive for some patients after drug exposure at high concentration, supporting the notion of drug resistance. Synergism between some of these drugs was evaluated in 3 samples, with some samples being more synergistic than other, requiring a larger number of samples. Conclusions: Cellular and molecular interactions between B-cells and the microenvironment represented here with the NLC, have become an attractive target for CLL therapy. Because novel drugs such as ibrutinib or idelalisib are transforming CLL therapy targeting the microenvironment, novel technologies that could predict its effect are necessary. Here we have adapted a Nurse-Like Cell assay mimicking the microenvironment published by Burger1 to our ExviTech platform. The automated platform enables scaling of the data points acquired with this assay supporting characterization of drug activity by pharmacological dose response curves, as well as exploring synergistic interactions. As showed in the results and illustrated in Figure 1, there is a interpatient variability of the pharmacological profile for the studied drugs, if clinically validated, could help guiding a personalized treatment selection; measuring the drug activity inside this particular microenvironment responsible of drug resistance. 1.- Burger JA et al. Blood. 2000 Oct 15;96(8):2655-63. Figure 1: Figure 1:. Disclosures Primo: Vivia Biotech: Employment. Martinez:Vivia Biotech: Membership on an entity's Board of Directors or advisory committees. Gorrochategui:Vivia Biotech: Employment. Espinosa:Vivia Biotech: Employment. Arroyo:Vivia Biotech: Employment. Ballesteros:Vivia Biotech: Employment. Hernandez:Vivia Biotech: Employment.

Description: Introduction: Despite the great medical advances associated with the introduction of thalidomide, bortezomib (BORT), and lenalidomide (LEN) for the treatment of multiple myeloma (MM), it remains an incurable disease. Most patients (pts) show disease progression, consistent with the clinical evolution of MM, and only a low percentage achieve long-term responses and extended progression-free survival (PFS). The heterogeneous nature of MM in both the clinical and biological setting is reflected in the heterogeneity of MM relapses. The International Myeloma Workshop Consensus Panel (Rajkumar, Blood 2011) states that treatment (Tx) shall begin either at clinical relapse with symptoms (clinR), or in the event of asymptomatic relapse with significant paraprotein relapse, biological relapse (BR). The purpose of this Spanish registry is to describe MM relapse patterns comparing the impact of Tx decisions in pts who meet the criteria for biological relapse (BR) according to IMWG criteria with those in whom Tx was delayed until clinical relapse (clinR). Here, the preliminary results of this study are presented. Methods: MM pts in (or previous to) first or second BR who have achieved ≥ PR since their last Tx are eligible for inclusion in this observational prospective registry at the time BR is detected. Evaluations performed at least bi-monthly are mandatory. A total of 41 Spanish sites participated in the registry following approval from their independent ethics committees, with 410 pts expected to be included, without physician’s decision of prescribing Tx affecting the inclusion. The main objective of the registry is to assess the time to progression (TTP) from the start of anti-MM Tx at the onset of asymptomatic BR vs. the start of Tx at the time of clinR. Secondary objectives are to describe demographics of BR; to assess the median time elapsing from BR to clinR; to assess overall response rate (ORR), event-free survival (EFS), PFS, overall survival (OS) at BR and at clinR (if appropriate); to asses safety and quality of life (QoL) using 2 validated questionnaires (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 and QLQ-MY24); to document the tolerability profile of the Tx; and to describe the use of associated resources. Here, we summarize baseline characteristics and preliminary results from 83 pts (out of 126 registered pts) who had basal data in the registry at the time of this report. Results: Overall, 79% of pts presented with a BR and 21% were in a bi-monthly watchful waiting follow up. The mean age of pts was 67 years, 53% were female, 57% were in first relapse, 43% and 27% had an ECOG performance status (PS) of 0 and 1, respectively, while the ECOG PS was unknown in 30% of pts at the time of this report. In total, 30% of pts had ISS stage I, 26% had ISS stage II, and 22% had ISS stage III, while ISS stage data were not available or unknown for 12% and 10% of pts, respectively. MM types were IgG Κ (37% of pts), IgG λ (23%), IgA Κ (13%), IgA λ (9%), and type was unknown in 17% of pts. 28% of IgG/IgA MM types were Bence-Jones. Cytogenetic risk assessments were available in 66% of pts. Among those pts with a BR, 51% received active Tx without waiting for a ClinR. First-line Tx was BORT-based in 70% of pts. Overall, 55% of pts had undergone autologous stem cell transplantation, 15% had received consolidation Tx and 34% had received maintenance Tx. After first-line Tx, 17% of pts achieved a stringent complete response (sCR), 31% achieved a CR, 24% achieved a very good partial response (VGPR), and 10% achieved a PR. The median time to BR was 24.53 months. Most (63%) pts who registered after second relapse received LEN-based Tx. Conclusions: To our knowledge, this is the first prospective study in MM to evaluate BR as well as the effects of Tx based on the decision to start Tx at BR vs. clinR. In this preliminary cohort, the physicians’ decision to start active Tx at BR, before the onset of clinR in 50% of cases, was noteworthy. Further follow-up is needed to identify the differences between these two strategies. Updated clinical results will be presented at the meeting. MM-BR Study, Spanish Myeloma Group-GEM/PETHEMA Bibliography Alegre A, et al. Haematologica. 2002;87:609-14. Brioli A, et al. Blood. 2014;123:3414-9. Fernández de Larrea C, et al. Bone Marrow Transplant. 2014;49:223-7. Lenhoff S, et al. Haematologica. 2006;91:1228-33. Rajkumar SV, et al. Blood. 2011;117:4691-5. Zamarin D, et al. Bone Marrow Transplant. 2013;48:419-24. Disclosures Alegre: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lahuerta:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Ruiz:Celgene: Celgene Stock options as part of the employee's compensation plan Other, Employment. Vilanova:Celgene: Contracted by Celgene Other.

Description: Introduction: Patients with type1 Gaucher's disease (GD1) have an increased risk of gammopathy (RR,33 Taddei TH 2009), multiple myeloma (RR,25.), other haematological malignancies (RR,3.45) and overall cancer risk (RR, 1.80). The Spanish Registry of Gaucher Disease (SpRGD) was established in 1993 in response to the need to group individual experiences in the diagnosis and management of this disease, increasing knowledge related to general characteristics and to know the real incidence and prevalence in the Spanish population. Registration is open to all physicians involved in the management of patients with GD and offers free enzymatic analysis, biomarkers and molecular analysis for the diagnosis and monitoring of patients (www.feeteg.org). Aim: to analyses the incidence of malignancies in adults GD patients. Patients and methods: A review of the SpRGD to obtain data form patients over 20 years of age at May, 2016 was performed. Physicians on charge fulfilled a survey in which they inform about the incidence of malignancies and follow-up information. Ethical approval was obtained from the institutional board and all patients has signed an inform consent before to be included into the SpRGD. Results: Of the 281 adult patients (³20 years) included, 279 were GD1 and 2 GD3. The average age of the entire cohort was 52.3 (23-90), of which 140 men, 141 women. Of these, 27 (9.6%) patients with GD1, 5 homozygous for N370S and 22 heterozygous for N370S had the presence of a malignancy and / or monoclonal gammopathy (MGUS), two of them had more than one neoplasia. Male / female: 11/16, mean age 60.2 (25-90), median follow-up of 16.5 years (4-23). Six have died by the tumor complications. All MGUS (N=12) were identified at GD diagnosis, they were 6 males and 6 females mean age 55.5 y (10-82) of them 50% under 60 years of age. Sixteen patients developed seventeen different neoplasms, with a female predominant (11, 68.7%). Only eight patients were under therapy at the time of neoplasia diagnosis (table1). Mean time on therapy 7.4 years (1.2-13-6). Neoplasms were registered (M/ F): B cell malignancies: Hodgkin lymphoma 1 (M), chronic lymphocytic leukemia 1 (M), multiple myeloma 1 (M), myeloid neoplasms: chronic myeloid leukemia: 1 (F), myelodysplastic syndrome: 1 (F), solid tumors: melanoma: 1 (F), meningioma: 2 (F), uterine cancer: 3 (F), gastric carcinoma 1 (F), cancer colon 2 (F), breast cancer 1 (F), prostate adenocarcinoma: 1(M), lung cancer 1 (M), liver carcinoma 1 (M), thyroid cancer 1 (F). Conclusions: It has been widely reported the highest incidence of haematological malignancies among patients with GD. Nevertheless in this cohort of Spanish patients, the incidence of solid tumors is similar to haematological neoplasms in general and higher than B cell lymphoid. Probably the incidence of malignancy in this population and during this monitoring period is similar to the expected in Spanish general population found in 0.21% / year, however females showed two times risk increase for malignancies and this aspect warranty further studies. This work has been carried out with aid for research FIS PS15/00616 and FEETEG Disclosures No relevant conflicts of interest to declare.

Description: Introduction Eltrombopag is an oral, non-peptide thrombopoietic receptor-agonist (TPO-RA). In chronic immune thrombocytopenic purpura (ITP) randomized–controlled trials proved to be effective, safe and well tolerated with reported response rates of 59%-88%. When eltrombopag is discontinued, platelet counts usually return to baseline within 2 weeks. However, certain patients may be able to discontinue TPO-RA and still maintain platelet counts above baseline without additional treatment. We report here 12 patients who presented sustained responses after discontinuing eltrombopag without substituting additional anti-ITP therapy. Patients and Methods Primary ITP was defined as a platelet count 〈 100 x 109/L in the absence of other causes or disorders that may be associated with thrombocytopenia. Patients received daily oral eltrombopag, at a starting dose of 50 mg/day adjusting the dose as needed up to a maximum of 75 mg/day based on the patient’s platelet count. Successful discontinuation of eltrombopag treatment was defined as a platelet count of 30,000/μl and 20,000/μl above initial baseline for at least 6 months off eltrombopag without substituting additional anti-ITP therapy. Results Our patients were 4 males and 8 females, with a mean disease onset age of 55 years (range, 28–79 years). The median time from diagnosis to eltrombopag start was 24 months (range, 1-480). 5 cases had ITP since less than 1 year. The median prior number of therapies was 5 (range, 1-7). All patients were refractory to corticosteroids. Six patients had received rituximab: Patient (P) 1, P2, P3, P6, P7 and P8. Seven patients were splenectomized. Three patients (P2, P6 and P8) who failed to respond to romiplostim were switched to eltrombopag. One romiplostim responder (P12) switched to eltrombopag because patient request. The median platelet count before starting treatment was 7 x 109/L (range, 1-97 x 109/l). At start, concomitant treatment was administered in 4 patients: P2, P3 and P9 corticosteroids. P5, intravenous immunoglobulin. The median maximum platelet count during treatment was 482 x109/l (range, 251-858 x109/l). One patient had a transient increase in leukocyte count reaching 12x109/L. The median duration of treatment was 5 months (range, 1-13) (Fig 1A): only one month in three patients. Nine patients stopped treatment due to platelets higher than 250 x 109/l. Initial stop of eltrombopag in P2 was failed because of low platelet counts and eltrombopag was reinitiated. After 8 months of re-treatment, eltrombopag could be stopped with no other treatments needed for over 6 months. In P1, P10 and P11 eltrombopag was stopped at 140, 178 and 138 x109/L platelets, respectively. After a median follow-up of 7 months (range, 6 – 20 months), ten patients maintain a platelet count greater than 100 x 109/L (Fig 1B) without any anti-ITP treatment. Discussion The possibility of eltrombopag cessation in a specific subset of patients has emerged. Recently, a prospective ongoing study has demonstrated that approximately 1/3 of patients (5 of 15) appear able to successful elective discontinuation of eltrombopag after 2 or more years of treatment. Nevertheless we have showed that the remission of ITP is feasible after short term treatment with eltrombopag (3 patients treated for only 1 month). Repeated short-term use of eltrombopag in chronic ITP has been reported. Patient P2 could succesfully reintroduce eltrombopag after initial treatment stop. In our data no factors predict which patients may discontinue eltrombopag. Disclosures: San Miguel: Jansen, Celgene Corporation, Onyx, Novartis, Millenium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees.