ALBERT

Description: Introduction. Elderly patients with chronic lymphocytic leukemia (CLL) and younger patients with comorbidities are often treated with chlorambucil (Chl), despite the relatively low response rates. The addition of anti-CD20 monoclonal antibodies to Chl substantially increases the response rates, without negatively affecting tolerability. Overall response rates (ORR) between 66% to 84% have been reported with these combinations, with complete responses (CR)ranging from 8% to 26%. Methods. We conducted a retrospective analysis on the use of the Chl-rituximab (R) combination as frontline treatment for elderly (≥65 years) and/or unfit (CIRS 〉6) CLL patients treated at 15 different Italian hematologic centers. The main aim of the study was to further establish the safety and efficacy of the Chl-R protocol and investigate whether certain CLL patients for whom this protocol could be particularly effective could be identified. To this end, we performed a subgroup analysis stratifying patients according to FISH and IGHV results: high risk group (HR) included patients with 17p deletion, intermediate risk group (IR) patients with 11q deletion and/or unmutated IGHV, low risk group (LR) patients without 11q or 17p deletion and/or unmutated IGHV. Results. One hundred and two patients who underwent treatment between 2009 and 2011 were enrolled in the study. Patients' clinical and biologic characteristics are summarized in Table 1. Three patients discontinued treatment earlier than planned: 1 for an episode of autoimmune hemolytic anemia (AIHA) that developed after the 2nd cycle of Chl and before starting R treatment and 2 patients for disease progression after the 3rd and 5th cycle of Chl-R, respectively. The median number of Chl and R cycles administered in the 102 patients was 8 (range 2-12) and 6 (range 1-9), respectively. The planned treatment schedule was different among centers: the two main schedules used were Chl administered at 1 mg/kg for each cycle every 28 days, given at a fixed daily dose of 10 mg starting from day 1 and repeated for 8 cycles, and Chl administered at 8 mg/m2/day for seven days of each of eight 28-day-cycles. R was added to Chl from the 3rd cycle onwards and was administered on day 1 of each cycle at a dose of 375 mg/m2 during the first administration and 500 mg/m2 for the subsequent 5 cycles. On an intention to treat basis, the ORR was 87.1%. Thirty-two patients (31.7%) obtained a CR and 56 patients (55.4%) obtained a partial response (PR). Nostatistically significant differences were noted in terms of ORR for age above or below 70 years, fitness status, ECOG, bulky disease, cytogenetic risk abnormalities, IGHV mutational status, ZAP-70 or CD38 expression.Median progression-free survival (PFS) and time to retreatment (TTR) were reached at 43.7 and 72.3 months, respectively. Median overall survival (OS) was not reached; 86.1% and 81.2% of patients were alive at 48 and 60 months, respectively. The most frequent serious adverse event was grade 3-4 neutropenia, occurring in 13.7% of patients. Grade 3-4 extra-hematologic side effects were uncommon (9.8%). Subgroup analysis of the LR and IR patients (no HR patients were enrolled) showed that LR patients had a significantly better PFS than IR patients (65.8 months vs 35.2 months, p=0.001; Fig. 1),with 54.9% of patients remaining free from progression 60 months after treatment. Conclusions. Treatment of elderly and/or unfit CLL patients with the Chl-R regimen is associated with low toxicity, a high ORR and durable PFS. Particularly good results are achieved in CLL patients with a mutated IGHV profile and not carrying both 17p and 11q deletion, suggesting that in this low-risk subset of unfit patients Chl-R could represent the optimal therapeutic option, in consideration of safety, efficacy and costs. Disclosures D'Arena: Janssen-Cilag: Honoraria. Coscia:Gilead: Honoraria; ROCHE: Honoraria, Other: Advisory board; Janssen: Honoraria; Mundipharma: Honoraria; Karyopharm: Research Funding. Molica:Jansen: Membership on an entity's Board of Directors or advisory committees; Roche Italy: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Speakers Bureau. Efremov:Gilead: Honoraria.

Description: Metastatic disease of the bone is a rare complication of chronic lymphocytic leukemia (CLL), it may be result from richter's transformation or metastatic from non lymphoid malignancies. CLL is the most common form of adult leukemia, with the median age of 70 years at diagnosis [Siegel et al. 2013]. The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes.The result is the increased number of lymphocytes in the peripheral blood, leukocytosis with absolute lymphocytosis, the increase of the lymphnodes, the increase in size of the spleen. The diagnosis of chronic lymphocytic leukemia B requires the presence of Clonal B cells in the peripheral blood at or above 5,000 / ul for at least 3 months. Typing immunophenotypical pathological lymphocytes are positive for surface antigens CD5, CD19, CD23, weakly positive for CD20 and CD22, generally negative FMC7 and CD79b; also expressing surface immunoglobulins. The Rai and Binet staging systems, which are established by physical examination and blood counts, have been recognized as standards for deciding whether to begin treatment. Patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. For fit patients, chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab represents the current standard therapy. For unfit patients, treatment with an anti-CD20 antibody (obinutuzumab, rituximab, ofatumumab) plus a milder chemotherapy (Chlorambucil) may be applied. At relapse, if the treatment-free interval exceeds two to three years, the initial treatment may be repeated, if the disease relapses earlier, drugs such as bendamustine (plus rituximab), alemtuzumab, lenalidomide, ofatumumab, ibrutinib, or idelalisib, must be choosen. Patients with a del(17p) or TP53 mutation can be treated with ibrutinib or a combination of idelalisib and rituximab. in relapsing patients with TP53 mutations or del(17p) or patients that are refractory to repeated chemoimmunotherapies, an allogeneic SCT may be considered [Hallek M 2015]. In this article we show a case of a 66-year-old man with CLL and a bone localization. In 2011 diagnosis of CLL, Rai Stage 0, Binet Stage A. Principal characteristics at diagnosis: HB 13.2 g /dl, White Blood Cells 15.800 / mm3, lymphocytes 61%, neutrophils 32%, monocytes 4%, platelets 141.000/mm3; normal hepatic end renal function; flowcytometric immunophenotyping of the peripheral blood revealed B-cell CLL; prognostic factors: CD38 negative, ZAP70 positive, rearrangement of the immunoglobulins mutated; FISH: negative; CT chest / abdomen / pelvis: presence of multiple aorto-pulmonary and axillary adenopathies (max diameter of 2 centimeters); bone marrow biopsy: infiltration of CLL equal to 60% of global cellularity. The patient was only observed until January 2015, when he was hospitalized due to acute anemia, requiring supportive therapy, and right foot pain . So it was decided to re-evaluate the whole disease in order to decide whether to start chemotherapy. The disease was staged again with instrumental and laboratory tests: presence of renal insufficiency, egd and colonoscopy negative, Coombs' test negative, bone marrow biopsy confirmed the diagnosis of chronic lymphocytic with bone marrow infiltration of 90%, abdomen ultrasound showed only moderate splenomegaly. On February, persistence of right foot pain and appearance of swelling, assessed by the orthopedic as a suspected algic and dystrophic syndrome. So he suggested to perform scintigraphy which revealed: pronounced inflammatory osteometabolic reaction of the right tibia/fibula/ankle third distal which could be referred, in the first evaluation, to algic and dystrophic syndrome. However, a local biopsy was performed: localization of chronic lymphocytic leukemia. On March 2015 a total body TC showed 2 nodular calcifications in the right lung lobe, multiple right paratracheal, barety space, aortopulmonary and axillary adenopathies. Prostate size increased. In order to study carefully the liver and prostate lesions, an ultrasound abdomen was performed that documented only enlarged spleen, normal size liver, free of focal disease, increased prostate due to symmetric bilobate hypertrophy . After the second cycle of chemotherapy, prolonged thrombocytopenia, so he continues only with a radiotherapy program. Disclosures No relevant conflicts of interest to declare.

Description: The aim of our perspective observational study was identify a fast molecular biomarker of tumorigenic-proliferative haematological disorders at on set using a non-invasive method. At this end, to better discriminate between myeloproliferative or lymphoproliferative hematological disease, from May to July 2014, we collected peripheral blood mononuclear cells (PBMCs) from patients at the first medical examination and without drug therapy. The patients were divided into groups on the basis of the diagnosis. Group 2 (n=8) included patients suffered from mixed disorders such as myeloproliferative neoplasms (MPD) associated to monoclonal gammopathy of undetermined significance (MGUS). Group 3 (n=8) included patients with only MGUS, group 4 included 9 patients with only primary myelofibrosis (M). Healthy donors (Group 1, n=16) were considered as normal subject or calibrator in molecular analysis. Their PBMCs were used to perform relativegene expression profile of a transcriptome involved in apoptotic control, stem-cell differentiation, immune network, inflammation and leukemogenesis, in order to detect whether these may serve to label the patient groups. A multigene expression assay (47 genes) was carried out with the TaqM,an® Low Density Array Fluidic card. In Group 3 (MGUS), 6 genes were differentially expressed (BMI-1, FLT3, FZD1, FZD5, ICAM1, IMP3). Also, we compared variance, main value for each gene in each group and T-test that showed a significant differential expression pattern (p

Description: BACKGROUND: The combination schedule of rituximab, fludarabine and cyclophosphamide is considered the standard therapy for fit and young untreated chronic lymphocytic leukemia (CLL) patients. However, although this therapy improves progression free survival (PFS) and overall survival (OS), it has been associated with increased toxicity: 76% of the patients experienced at least one grade 3 or 4 event. Recently, encouraging clinical results in terms of safety and efficacy have been obtained using bendamustine in combination with rituximab (R-B) in untreated CLL patients. PURPOSE: We performed a multicentre retrospective study to assess safety and efficacy of R-B in a large group of untreated CLL patients. METHODS: One hundred and thirty six untreated CLL patients were recruited from 16 Italian Institutions and included in the present analysis. The median age was 69 years (range 43–85), with 49.3% of patients older than 70 years; 53.7% of cases were male. All patients had active disease as defined by the NCI-WG, and 27.2% were at Binet stage C. FISH data, available in 86/136 cases, identified a del(17p) in 5.1% of the patients and del(11q) in 5.9%. Sixty-four patients (47.1%) had a creatinine clearance ≤70 mL/min. Fifty-six % of cases showed a WHO performance status (PS) of I-II and 61% a CIRS comorbidity index 〉0. RESULTS: Among the 136 patients, 90 cases (66.2%) received B at the dosage of 90 mg/m2 on day 1 and 2 every 28 days, the remaining 46 cases received B at the dosage of 70 or 80 mg/m2. R was administered at the dosage of 375 mg/m2 on day 1 of all cycles in 59.6% of cases, while 40.4% received 375 mg/m2 on day 1 of the first cycle and 500 mg/m2 on day 1 of the other cycles. A total of 725 cycles were administered with a median number of 6 cycles per patient. Eighteen patients (13.2%) required early discontinuation of therapy before the sixth cycle for serious infections (n=7), persistent hematological toxicity (n=5), grade 4 dermatological toxicity (n=3), withdrawal of consent (n=2), hypersomnia and depression (n=1). Grade 3 or 4 adverse events for neutropenia, thrombocytopenia, and anemia were documented in 25.8%, 25.8%, and 16.2% of patients, respectively. Grade 3 or 4 severe infections occurred in 6.6% of patients. The overall response rate (ORR) was 93.4%, 48 patients (35.3%) achieved a complete response (CR), 79 (58.1%) a partial response (PR), 8 (5.9%) a stable disease (SD) and in 1 patient (0.7%) no response assessment was performed due to death prior to terminating therapy. In the high-risk group with del17p, 5/7 (71.4%) cases achieved a PR and 2 a SD. Age 〉70 years (P=0.026) and del17p (P=0.007) were the only two parameters significantly associated with a lower response rate, while del11q and unmutated IGHV, as well as creatinine clearance 0 did not seem to impact on achievement of response. The only parameter predictive of the probability of achieving a CR was an age

Description: Abstract 2462 Background: Two of the largest trials ever conducted in patients with chronic lymphocytic leukemia (CLL) have shown that the addition of rituximab to fludarabine plus cyclophosphamide (R-FC) significantly improves outcome. However, myelotoxicity and immunosuppression limit the use of this regimen in patients with impaired performance status and pre-existing co-morbidities, predominantly in the elderly. Chlorambucil (CLB) remains a first-line treatment option for such patients. The use of CLB in combination with R is thus an attractive therapeutic option in view of the potentially increased activity compared to CLB alone and the likely good tolerability. This study was designed to determine whether the R-CLB combination is feasible and beneficial as first-line treatment for elderly patients with CLL and to define the role of maintenance R. Patients and Methods: Between October 2008 and January 2010, 97 elderly patients with untreated CD20+ CLL requiring therapy according to the IWCLL criteria were enrolled into the protocol. CLB treatment was administered every 28 days for up to 8 courses at a dose of 8 mg/m2/day p.o. on days 1–7 combined with 375 mg/m2 R for cycle 3 and 500 mg/m2 for cycles 4–8. Responsive patients were randomized to R maintenance (375 mg/m2 every 2 months for 2 years) versus observation. At baseline, blood samples were taken for FISH analysis, IgVH mutational status and expression of Zap-70 and CD38. Minimal residual disease (MRD) was planned to be evaluated on peripheral blood (PB) and bone marrow (BM) cells by four-color flow cytometry and, when required, by PCR. The primary endpoint was the overall response rate at the end of the induction phase defined according to the IWCLL 2008 on the intention-to-treat (ITT) population (all enrolled patients who received at least 1 dose of R). Secondary endpoints included the adverse event (AE) profile, progression-free and overall survival. Results: These are the data of the planned interim analysis based on the first 54 evaluable patients from 19 Italian centers, including tumor response at the end of the induction phase and safety. The median age of patients was 70.5 years (range 61–84): 14.8% were between 61 and 64, 31.5% between 65 and 69, 31.5% between 70 and 74, 16.7% between 75 and 79, and 5.6% were ≥80 years; thus, 53.8% of patients were over the age of 70; 70.4% were males; 25.9% were Binet stage A, 57.4% stage B and 16.7% stage C. The overall incidences of trisomy 12 and abnormalities of 13q, 11q23 and 17p13 were 24.5%, 52.8%, 20.8% and 5.7%, respectively; 7.5% of patients had p53 mutations. Of the 51/54 patients analyzed for the IgVH mutational status, 64.7% were unmutated; of the 53/54 patients studied, 39.6% were CD38+ and 71.7% were Zap-70+. The overall response rate on an ITT analysis was 81.4% (44/54 patients); a CR assessed by CT scan and trephine immunohistochemistry was found in 16.7% of cases (9 patients: 4 in Binet stage A, 3 in stage B and 2 in stage C), a CRi in 3.7% (2 patients), a nPR in 1.9% (1 patient) and a PR in 59.3% (32 patients). Eight of the 9 CR cases were investigated for MRD by flow cytometry and all proved positive: 6/8 had MRD levels

Description: RI is a common and severe complication throughout the course of MM. Vel, either as single agent or combined with other drugs, has been shown to be highly active in MM pts with varying degrees of RI. We retrospectively analyzed the outcome of 105 pts with RI (CrCl

Description: The front-line therapy for CLL young and fit patients is chemo-immunotherapy with Fludarabine-Cyclophosphamide and Rituximab (FCR). However, around three quarter of the patients with a newly diagnosed CLL are 65 years or older, with approximately 42% being older than 75 years and with age-related comorbidities. FCR regimen results in a significant myelosuppression and high rates of early and late infections. Hence, other less toxic regimens are under evaluation. Recently the German CLL study group reported an interim analysis of the CLL10 trial, who compared FCR vs Bendamustine-Rituximab (BR). The response rates to the 1st-line treatment with BR or FCR were comparable, and BR could be an alternative 1st-line treatment for medically fit pts. Notably, this study showed that pts treated with BR were often older (median 71 vs. 65 yrs; p 7). All patients had an ECOG performance status ranging from 0 to 2. Twenty-nine of 70 patients had Binet stage C, 12 patients were Binet A, 29 Binet B. Thirty-nine patients showed karyotype abnormalities at FISH analysis (data available in 54/70 patients). High risk FISH karyotype according to Döhner´s hierarchical model was detected in 17 patients (14 with del 11q, 3 with del 17p). Ten of them had del(13q14), 12 had trisomy 12 and 15 had normal karyotype. The analysis of the IGHV status, available in 50 patients, showed 25 patients with somatic mutation and 25 patients with germ-line sequences. Zap-70 data were available for 37/70 pts, 19 of them (51.3%) were Zap-70 positive. CD38 was available for 52 patients: it was positive in 27/52 pts (51.9%). (Table 1) A mean number of 5.46 courses of BR were given and the Bendamustine dose was reduced by more than 10% in 39 patients (55,7%). The main reason for dose reduction was haematological toxicities. The ORR rate was 88,6%,with 22 patients (31.4%) obtaining a CR and 40 patients (57,2%) obtaining a PR. Progression Free Survival, Time To Retreatment and Overall Survival rates at 2-years were 79%, 90.3% and 89.6%, respectively. Only the presence of del17 resulted to affect the response rate (p= 0.023) and PFS (p7 8/70 pts (11.4%) PB lymphocytes 33.203/mmc Binet stage A 12/70 pts (17.2%) Binet stage B 29/70 pts (41.4%) Binet stage C 29/70 pts (41.4%) ZAP70〉20% 19/37 pts (51.3 %) CD38〉 30% 27/52 pts (51.9%) Beta2microglobulin increased 51/59 pts (86.4%) IgVH homology 〈 98% 25/50 pts (50%) Normal FISH 15/54 pts (27.8%) del 13q 10/54 pts (18.5%) +12 12/54 pts (22.2%) del 11q 14/54 pts (25.9%) del 17p 3/54 pts (5.6%) Bulky syndrome 16/70 pts (22.9%) PB, peripheral blood; IgVH, immunoglobulin heavy chain variable genes; FISH, Fluorescent In Situ Hybridization. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 294 Rituximab plus fludarabine/cyclophosphamide (R-FC) is currently the standard of care for fit patients with untreated or relapsed CLL. However, patients with CLL are predominantly an elderly population and many of these patients may have comorbidities that make them less suitable to receive fludarabine-containing therapy. Chlorambucil-based treatments are frequently used for these patients despite the fact that clinical benefits are limited. There is a need for well-tolerated and more efficacious treatment regimens for these patients. The ML21445 study evaluated the combination of rituximab and chlorambucil (R-chlorambucil) as first-line treatment for patients with CLL considered ineligible for treatment with the current standard of care, R-FC. Patients aged 〉65 years (or 60–65 years and ineligible for fludarabine) were treated with eight 28-day cycles of chlorambucil (8 mg/m2/day Days 1–7) with rituximab administered on Day 1 of cycle 3 (375 mg/m2) and cycles 4–8 (500 mg/m2). Patients with a response at the end of induction were randomized to rituximab maintenance therapy (375 mg/m2 every 8 weeks for 2 years) or observation. The induction phase of the study is complete while the maintenance phase is still ongoing. The overall response rate (ORR) in 85 patients who received at least one dose of rituximab during induction was 81.2% (n = 69) with 16.5% (n = 14) achieving a complete response (CR) and 2.4% (n = 2) a CR with incomplete bone marrow recovery (CRi). ORR and CR rates were similar across the different Binet stages (ORR: Binet A 86.4%, Binet B 79.6%, Binet C 78.6%) and age categories (ORR: 60–64 years 84.6%, 65–69 years 85.2%, 70–74 years 75.0%, ≥75 years 81.0%). Two of four patients aged ≥80 years responded to induction treatment. Logistic regression analysis revealed no correlation between known biological prognostic factors – CD38, cytogenetics, IGHV mutational status, ZAP-70, thymidine kinase, soluble CD23, and beta-2 microglobulin – and response to treatment. To further investigate possible factors influencing response, pre-treatment patterns of gene expression were analyzed in different patient subgroups. Material was available for 62 patients, including 16 with CR/CRi, 41 partial responders and 5 non-responders. In an exploratory analysis, mRNA expression was examined using Affymetrix® Human Genome U133 microarrays. This revealed marked differences in pre-treatment gene expression profiles between response groups. Non-responders showed a homogeneous gene expression signature involving up-modulation of transcripts involved in anti-apoptotic and pro-proliferative pathways, including K-ras and N-ras. CR/CRi patients also showed a homogeneous pattern of gene expression that was clearly distinct from non-responding patients, while patients with a partial response showed a more heterogeneous pattern of gene expression before treatment. These initial findings reflect the heterogeneity of CLL and suggest that microarray analysis of gene expression may be useful in predicting response to R-chlorambucil in elderly patients with CLL. Disclosures: Foa: Roche: Consultancy, Speakers Bureau. Cuneo:Roche: Consultancy, Speakers Bureau. Montillo:Roche: Membership on an entity's Board of Directors or advisory committees. Alietti:Roche: Employment. Runggaldier:Roche: Employment. Gamba:Roche Italia: Employment.

Description: Hepatitis C virus (HCV) is a global health infection that affects about 170 million persons worldwide an it is the principal cause of chronic live-diseases. Progression to chronic disease occurs in the majority of HCV-infected persons, and infection with the virus has become the main indication for liver transplantation. Initial diagnosis of HCV infection is classically done by serologic methods either by determining anti HCV antibody and by determining the presence of HCV RNA . HCV encodes a virus-specific helicase, protease, and polymerase, and because of the critical function of these proteins in the viral life cycle, they represent attractive targets for antiviral therapy. Multiple myeloma (MM) is a plasmacell neoplasm. The diagnosis is performed on bone marrow aspirate or bone marrow biopsy that show the presence of plasmacells, associated to anemia, hypercalcemia, osteolytic bone lesions, real failure ( C.R.A.B features). It is important distinguish between monoclonal gammopathy of undetermined significance, asymptomatic (smoldering) multiple myeloma, symptomatic multiple myeloma, solitary plasmacytoma, and other plasma cell diseases based on the IMWG criteria . Diagnosis should be based on the following tests: detection and evaluation of the monoclonal (M-) component by serum and 24-h urine protein electrophoresis; quantification of IgG, IgA and IgM immunoglobulins; characterization of the heavy and light chains by immunofixation; serum-free light-chain measurement, evaluation of bone marrow plasma cell infiltration; evaluation of lytic bone lesions, through full skeleton X-ray survey or magnetic resonance imaging (MRI); biological assessments (b2-microglobulin, C-reactive protein, lactate dehydrogenase and serum albumin); cytogenetic and fish analysis, haemoglobin (and full blood cell counts), serum creatinine and calcium level. Bortezomib is the drug used as first line therapy. It is a proteasome inhibitor. During treatment with bortezomib, rare cases of hepatic failure have been reported . lenalidomide is used an second line therapy , it belongs to the immunomodulatory drugs (IMiDs). No dedicated study has been conducted in patients with hepatic impairment, as the elimination of unchanged lenalidomide is predominantly by the renal route. In this article we report a case of a 74-year-old women with MM and HCV-related disease treated with bortezomib and lenalidomide. In 2008 diagnosis of MGUS. From 1976 Hepatitis HCV-related disease after transfusion. During this period periodic abdominal ultrasound showed steatosis of liver and an increase of transaminases. No need of liver biopsy. In July 2011 it showed evolution in Multiple Myeloma. Stage IIA according to Durie and Salmon Stage, I Stage according to ISS Stage System. Principal characteristics at diagnosis: PLT 73.000/mmc, Hb 9.6 g/dl, WBC 4.100/mmc, Plasmacells 33%, SGOT 120 U/L , SGPT 93 U/L, Creatinine 1 mg/dl, IgG 3060 mg/dl, Calcium 8.4 mg/dl, Gammaglobulin 34.7%, Monoclonal Component 3.1 g/dL, Serum Immunofixation IgG-Lambda, Urine Immunofixation Negative, Scheletal Survey Negative, MRI Negative, FISH Negative, Cytogenetics Negative, HCV-RNA 5.120.000 UI/ml. No antiviral therapy with acyclovir. So the patient was treated with bortezomib (1,3mg/m^2) and dexamethasone (20mg) day 1,8,15,22. After 9 cycles of therapy, completed in August 2012, the patient obtained a VGPR (Very Good Partial Response), with an improvement of liver parameters and of the blood counts. SGOT 36 U/L, SGPT 35 U/L, HCV-RNA 2.120.000 UI/mL, PLT 90.0000/mmc. In August 2013 progression of the disease ( HCV-RNA 4.000.000 UI/mL) so the patient started therapy with lenalidomide (25 mg) and steroids dexamethasone 20 mg), still ongoing. Currently normal liver parameters and blood counts. The last HCV RNA value is 1.390.000 UL/ml. The efficacy of bortezomib and lenalidomide in multiple myeloma is known to everyone. In this report, we want to show that, although the patient has been affected by HCV-related liver disease for many years, treatment with bortezomib and lenalidomide allows to obtained a good response to myeloma. Moreover, despite the effectiveness of acyclovir is recognized in the literature in terms of reducing the hepatitis C virus , the HCV RNA value is decreased during treatment with bortezomib and lenalidomide without the use of it. Furthermore, the combination with steroids did not worsen the hepatic pathology. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 2471 Eighty-one previously untreated CLL patients, ≤60 years, with advanced/progressive disease were included in the GIMEMA LLC0405 prospective multicenter study. Patients were stratified according to the biologic features. High risk (HR) patients were defined by the presence of: 1) 17p- (≥20% of analyzed cells), or 2) 11q- with ≥1 additional unfavorable factor (IGHV germline; Zap-70+ ≥10%; CD38+ ≥7%), or 3) germline IGHV or mutated VH3-21 and ≥2 unfavorable factors (Zap-70; CD38; 6q-; trisomy 12). Low risk (LR) patients were defined by the absence of the above features. HR patients received 4 monthly courses of fludarabine and campath-1H (FluCam; Flu 30 mg/m2 iv; Cam 30 mg iv, days 1–3). Responding patients underwent post-induction therapy: reduced intensity PBSC allogeneic transplant or, in the absence of a sibling donor, an autologous PBSC transplant or, in the absence of a sufficient harvest, Cam sc, 30 mg weekly for a maximum of 12 weeks. For LR patients, treatment included 6 monthly courses of fludarabine and cyclophosphamide (FC; fludarabine 30 mg/m2 iv and cyclophosphamide 250 mg/m2, days 1–3). All patients received bactrim prophylaxis. FluCam-treated patients underwent weekly CMV antigenemia monitoring and valacyclovir prophylaxis (2g/8h). In the presence of severe granulocytopenia, G-CSF was recommended and darbepoietin given in case of anemia (Hb