ALBERT

Description: Background Acute promyelocytic leukemia (APL) in the elderly has a favourable outcome in a significant proportion of patients (pts). Elderly and frail pts are usually treated with attenuated treatment schedules, mostly "according to medical judgment". The combination of all-trans retinoic (ATRA) and anthracycline-based chemotherapy (CT) has been the mainstay of treatment for many years. Alternative approaches, such as arsenic trioxide (ATO) and gentuzumab ozogamicin (GO) have recently been tested with success in this setting, even though no large series of elderly pts treated with CT-free first-line treatment have been published yet. Moreover, neither a "standard of care approach" nor a specific prognostic score system have been developed to guide physician in choosing the most adequate treatment schedule in this setting. Objective Aim of the present preliminary survey was to assess genetic and clinical features of APL in pts over 60 yrs. This cut off reflects the definition of "elderly patient" in most Italian APL GIMEMA trials. Moreover, both the real life outcome and safety data after either conventional anthracycline-based CT or alternative CT-free approaches were analysed. OS, response rate to either regimens and adverse event occurrence were collected. Methods This retrospective multicenter REL (Rete Ematologica Lombarda) survey, enrolled a total of 101 consecutive APL pts aged ≥60, treated between 2000-2018. Demographics, clinical data and therapy outcome data were recorded in a dedicated patient's report form. Statistical analysis was performed using the Kaplan Maier method, Log-rank test and Cox regression. Results For analysis, pts were grouped into different categories according to age and fitness. Tables 1 and 2 summarise clinical charcteristics and treatment administered. Performance status (PS) and number of comorbidities increase with age. Twentynine of 102 (28,4%) and 9/102 (8,8%) pts had a history of or subsequently developed a solid tumor respectively. High frequency of additive cytogenetic abnormalities was observed as well. CT+ATRA was preferentially administered, mostly with attenuated intensity, to younger pts with better PS, while ATO+ATRA was preferred in pts with reduced cardiac function and ATRA monotherapy was reserved to frail or over 80 yrs old pts. Rates of differentiation syndrome or infections or cardiac events were similar in the different treatment groups. Overall, complete remission (CR) rate after induction therapy was 94.16% [CI95%: 87,5%-97,8% ]. At a median follow-up of 40 mos (range 0-199), the overall relapse rate was 24%. Median time to relapse was 7 mos in 1/8 (12,5%) ATRA monotherapy treated pts and 13 mos (range 5-66) in the 23/68 (33,8%) pts receiving CT+ATRA. No relapse occurred among the 22 pts treated with ATO+ATRA (p 0.005). OS and EFS were significantly associated with pts' age (HR 9% and 7.6%; p

Description: Background: NMS-03592088 is a novel, potent inhibitor of the FLT3, CSF1R and KIT receptor tyrosine kinases (KD 〈 1 nM for all three targets). The compound demonstrated high preclinical efficacy following oral administration in all tested target-dependent tumor models, including those harboring kinase domain secondary resistance mutations, such us the FLT3 residue 691 gatekeeper mutation and the KIT residue 670 and exon 17 mutations. In a FLT3-ITD model of disseminated AML, efficacy observed following single agent treatment with NMS-03592088 was further significantly increased when administered in combination with cytarabine, with excellent tolerability. In preclinical studies conducted in non-human primates, a dose-related increase of circulating CSF1 levels was observed in association with the administration of NMS-03592088, consistent with in vivo inhibition of CSF1R by the compound, thus providing the opportunity for the use of CSF1 levels as a potential pharmacodynamic biomarker of CSF1R modulation in the clinical setting. All three targets of NMS-03592088 are relevant in different settings of hematologic malignancies and solid tumors. In particular, FLT3 mutations occur in approximately 30% of acute myeloid leukemia patients (AML), and are associated with a poor prognosis; KIT mutations are reported in patients with the core-binding factor (CBF) subtype of AML and the CSF1 and/or CSF1R genes are frequently expressed in AML blasts. Recent experimental evidence suggests a potential therapeutic rationale for CSF1R blockade in AML, possibly due to interference with microenvironmental support [Edwards DK et al, Blood, 2019, 133: 588]. Furthermore, chronic myelomonocytic leukemia (CMML) blasts express high levels of CSF1R and NMS-03592088 was able to effectively inhibit their proliferation, concomitant with the suppression of intracellular CSF1R dependent signalling. A clinical trial exploring safety, tolerability and efficacy of NMS-03592088 in patients with AML and CMML is therefore warranted. Trial design: This first-in-human study (EudraCT Number: 2018-002793-47) is designed as an open-label multicenter Phase I/II trial including patients with relapsed or refractory AML or CMML who have exhausted standard treatment options, or for whom standard therapy is considered unsuitable. The study is designed to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and to explore the preliminary anticancer activity of NMS-03592088 administered orally as single agent once daily for 21 consecutive days, followed by a 7-day break within a 28 day cycle. The study includes an initial conventional phase I part with an accelerated dose titration design in subsequent cohorts of 3+3 patients aimed at defining the maximal tolerated dose (MTD) and the recommended phase 2 dose (RP2D), followed by a limited dose expansion to confirm the RP2D. Once the RP2D is confirmed, a single-stage exploratory Phase II part will start comprising two parallel cohorts, one cohort will consist of AML FLT3 mutated patients and one of patients with CMML. Patients previously treated with FLT3 inhibitors are allowed to participate. The primary endpoint of the Phase II portion of the study is Overall Response Rate. Efficacy will be assessed according to standard criteria [Döhner H et al, Blood 2017, 129: 424; Savona MR et al., Blood, 2015, 125: 1857]. Exploratory endpoints are included to evaluate the potential effects of treatment with NMS-03592088 on circulating levels of CSF1 in plasma, the potential correlation of cellular CSF1R expression levels with clinical outcome in both AML and CMML, and the mutational status of a panel of leukemia-related genes, not limited to FLT3. The Phase I part started in Italy in March, 2019 and is currently ongoing. Disclosures Ciomei: NMS: Employment. Zanetta:Clioss: Employment. Fiorentini:Accelera: Employment. Bosotti:NMS: Employment. Ardini:NMS: Employment. Lombardi Borgia:NMS: Employment. Pulci:Accelera: Employment. Gatto:Clioss: Employment. Di Sanzo:Clioss: Employment. Colajori:Clioss: Consultancy. Davite:Clioss: Employment. Galvani:NMS: Employment. Gan:NMS: Employment. Rossi:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Mundipharma: Honoraria; BMS: Honoraria; Sandoz: Honoraria; Daiichi-Sankyo: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees. Rambaldi:Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, travel support; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Italfarmaco: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Omeros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Isacchi:NMS: Employment.

Description: α and β-tryptase genes cluster on the short arm of human chromosome 16 and encode lineage-associated serine proteases that are abundantly expressed in mast-cells and, in trace amounts, in basophils. Under physiologic conditions no other myeloid cells express tryptases. However, in several myeloid leukemia cell lines and in AML blasts, the level of tryptase is elevated. In an attempt at correlating the levels of tryptase with cytogenetic features and the KIT and FLT3 mutational status, we analyzed serum samples collected at diagnosis from 150 AML and 57 ALL adult patients. The total serum concentration was determined by UniCAP 100 and UniCAP Tryptase Fluorenzyme Immunoassay Kit (Pharmacia-Upjohn, Uppsala, Sweden). The median value of tryptase level in the control group (50 healthy people; mean age 35 y, range 20–50; M/F= 26/24) amounted to less than 5 ng/ml, ranging from 1 to 15 ng/ml. We detected elevated tryptase levels (more than 15 ng/ml) in 66 out of 150 AML-patients (44%) and in 1 out of 57 ALL-patients (1.75%; median value 1.2 ng/ml) (p = 〈 0.0005, Fisher’s exact test ). In AMLs data showed that elevated tryptase values are significantly bound to patients with t(8;21) (n = 26, p =

Description: Introduction Several studies have recently pointed out the adverse impact of KIT mutations (mutKIT) on relapse incidence (RI) and overall survival (OS) in AML pts with t(8;21). By contrast, the prognostic significance of mutKIT in pts with inv(16) remains unclear. Purpose of this study is to evaluate the prevalence and the prognostic impact of mutKIT in inv(16)(p13q22). Patients and Methods Fifty adults with inv(16) AML at diagnosis (median age 46.6 yrs, range: 17–88; M/F: 30 /20), were centrally analyzed for mutKIT in exon 2, 8, 10, 11 and 17. Mutations were detected using sequencing and other sensitive assays such as ARMS (amplification refractory mutation system) PCR for D816Y and D816H and enzymatic digestion with HINFI for D816V and with Tsp509I for N822K. Results Data showed a prevalence of KIT mutation of 34% (17/50 pts). Among the mutKIT cases, we detected mutations in exon 17 (n=12), exon 8 (n= 4) and exon 10 (n=1). There was no difference between the mutKIT vs the unmutated (KIT-) patients in the median of WBC count at presentation (WBC 13.9 x109/L, range 4.4 to 277.5 vs 19.4 x109/L, range 2.5 to 130; Mann-Whitney U test: p = 0.649). Of the 42 patients (age 〈 60 years) who received intensive chemotherapy, 13 resulted mutKIT upon mutational screening. Complete remission (CR) was achieved in 13/13 (100%) mutKIT vs 27/29 (93%) KIT- patients (Fisher’s exact test: p 〉 0.999). At a median follow-up of 26 months (range: 2–144), 9/13 (69%) mutKIT and 8/27 (29%)KIT- pts relapsed;the Kaplan-Meier plots revealed KIT mutations to be a significant factor adversely affecting RI (log-rank test: p = 0.017) but not OS (61% in mutKIT vs 75% in KIT-;log-rank test: p = 0.331). Conclusion KIT mutations are associated with a greater probability of relapse following CR, without affecting OS, in AML pts with inv(16) aged

Description: Abstract 3120 Introduction Fluorodeoxyglucose positron emission tomography (FDG-PET) is a functional imaging tool routinely used for staging and response assessment in aggressive lymphomas. Even if mantle cell lymphoma (MCL) is considered FDG avid, current data on the use of PET in this histotype are scant. We retrospectively analysed 43 PET scans in 22 MCL patients (pts) and compared the results to standard contrast-enhanced computerized tomography (CT) in order to define PET sensitivity and specificity in this rare lymphoma. Patients and methods Twenty-two pts with biopsy proven diagnosis of MCL underwent PET in different phases of disease for a total of 43 scans. PET scans were co-registrated with a simultaneous CT and compared to standard contrast-enhanced CT performed within 4 weeks. Nineteen PET (44.2%) were performed for disease staging at diagnosis or relapse, while 24 (55.8%) for response assessment. Negative PET were included in the analysis for response assessment only if a previous positive scan was available. Results PET and standard CT results were concordant in 16/43 cases (37.2%). Discrepancies were found in 27/43 cases (62.8%) and were grouped in four categories: false negative PET (5 cases), PET positive with a disease extension minor or major than CT (7 and 9 cases, respectively) and PET positive with negative CT (6 cases). At staging PET was concordant with CT in 4/19 (21%) cases. In 5/19 cases (26.3%) PET was negative in all disease sites documented by standard CT. In the remaining 10 cases (52.7%) PET was positive but discordant with disease extension evaluation by CT, determining upstaging and downstaging in 5 scans (26.3%) each. Involvement of gastro-intestinal tract was detected only in 4/19 cases (21%). PET performed for response assessment was concordant with CT in 12/24 cases (50%). In 6/12 concordant cases (25%) both CT and PET were negative; in the remaining 6/12 cases (25%) PET was positive and disease extension evaluation was concordant with standard CT. Six out of 12 discordant cases (25%) presented different disease extension evaluation; in the other six cases standard CT was negative while PET documented minimal residual disease (MRD). PET sensitivity and specificity in the entire cohort were 86.5% and 100%, respectively; positive predictive value was 100%, while negative predictive value was 54.5%. No difference in PET sensitivity was found in nodal and extra-nodal sites. No statistical significant correlation was found between PET sensitivity and proliferation index; nevertheless, no pts with Mib-1〉50% presented either false negative PET scan or disease extension underestimated by functional imaging. Conclusion This analysis shows a PET sensitivity (86.5%) lower than expected if compared with other aggressive lymphomas. High specificity registered in this cohort is likely to be ascribed to simultaneous CT co-registration, that allows identification of false positive cases. A false negative PET scan at initial staging was registered in 21% of cases. A gastro-intestinal tract involvement, expected to be near universal in advanced stage MCL, was detected by functional imaging only in 21% of pts at disease onset or relapse. Either downstaging or upstaging of disease burden seldom result in different therapeutic approach since localized MCL is a rare entity. Minimal residual disease, detected by functional imaging in half of standard CT negative pts at response assessment, has uncertain role in MCL, since the disease remains incurable and there is no clear evidence that MRD positivity requires treatment. All these findings advise against utilization of functional imaging for routine management of MCL. Considering heterogeneity of FDG-uptake in MCL, PET is likely to be more reliable in pts presenting high proliferation index. Moreover, current data suggest a prognostic value of baseline FDG-avidity. Further investigations are needed to confirm these preliminary data in larger prospective trial, separating MCL from other aggressive histotypes. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 2934 Poster Board II-910 Background: hepatitis C virus (HCV) infection has been associated with increased risk of developing B-cell lymphoprolipherative disorders through chronic immune stimulation. Discordant data have been reported about the prevalence of HCV infection in patients with Waldenström's Macroglobulinemia (WM) and the putative role of HCV in lymphomagenesis of this non-Hodgkin Lymphoma subtype remains controversial. Aim: the current retrospective study was conducted to assess the impact of this infection itself in the clinical and biological features and outcome among WM patients as compared with those with HCV negative WM. Patients and methods: we analyzed 140 WM patients with tested anti-HCV antibody (HCV-Ab). HCV-Ab positivity was detected in 21 cases (15%). Clinical characteristics of patients at diagnosis of WM are reported in the table below. Results: HCV positivity was correlated to lower counts of platelets, neutrophil granulocytes, haemoglobin and with presence of cryoglobulins or autoantibodies and splenomegaly. Interestingly we even found a strong link between the presence of HCV and serum parameters of tumor burden such as beta-2 microglobulin (B2-M) and lactate dehydrogenase (LDH). Furthermore we did not reveal any outcome implications in terms of disease progression needing treatment, time from diagnosis to first therapy, overall survival between HCV- and HCV+ patients. Overall, 88 patients (63%) received treatment for disease progression with schedules including Rituximab in 46 cases (52% of treated patients). Rituximab was administered even in HCV-RNA positive patients associated to Cyclophosphamide and Fludarabine and this did not translate in hepatitis development. HCV-RNA was strictly monitored during immunotherapy and we did not observe any significant flair. Conclusions: in our series of patients HCV infection does not seem to affect clinical outcome of disease. Moreover, in our experience patients with documented infection can receive the same schedule of treatment including intensive chemotherapy even with monoclonal antibodies without development of further toxicity. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 966 Backgrounds Previous in vivo and in vitro studies have highlighted the activity of Lenalidomide (Len) in patients with relapsed or refractory mantle cell lymphoma (MCL), achieving a 53% overall response rate (ORR), which included 20% complete responses (CR) (Habermann et al. Br J Haematol. 2009) and the possible synergistic anti-proliferative effect of Dexamethasone (Dex). Purpose: On this basis we performed a prospective, multicenter, phase II study, to evaluate safety and efficacy of Len Dex combination for adult patients with MCL. Patients and Methods Patients had to have ≥1 prior treatment regimen, and were either not eligible for, or had relapsed after, more intensive treatments including stem cell transplantation (SCT). During the induction phase (month 1 to 3), patients received Len 25 mg/day on days 1 to 21 and Dex 40 mg/day on days 1, 8, 15, 22 of a 28-day cycle (Len Dex). Enoxaparin 4000 U/day was administered as anti-thrombotic prophylaxis. Patients who achieved a partial response (PR) or stable disease (SD) at the end of the induction phase continued to the consolidation phase, which consisted of treatment with Len Dex until disease progression or unacceptable toxicity, for a maximum of 12 months. Patients with a CR at the end of the induction phase, or those who achieved a CR during consolidation, received an additional 3 courses of Len Dex. The primary objective was to evaluate the ORR and CRR. Response data were correlated with the modification of angiogenic biomarkers by analyzing immunohistochemistry macrophage infiltration and the bone marrow (BM) microvessel counts, and by measuring plasma levels of VEGF, bFGF and HGF before and after therapy. Results Between July 2008 and July 2009, 33 patients were enrolled on this study. Patients' median age is 68 years (range 51–80); 30 have the classic histology while 3 patients have the blastoid variant; 10 patients previously received two lines of therapy, 10 patients had three lines and 13 patients had 〉3 prior lines (median 3; range 1–7). Twelve patients previously underwent an autologous SCT and 8 received prior therapy with Bortezomib. The number of patients who responded to induction phase was: OR= 22 (67%) including 5 CR (15%), SD= 1 (3%), no response (NR) or progression (PD)= 10 (30%); OR in patients previously treated with Bortezomib or an autologous SCT was 50% each. At present, 13 patients completed the therapeutic program, 15 discontinued therapy prematurely (14 NR or PD, 1 poor compliance) and 5 remain on therapy. The final response status at the end of the therapeutic program is: OR= 18 patients (55%) including 8 CR (24%), NR/PD= 15 (45%). After a median follow-up of 6 months (range 3–13 months) from the end of therapy, none of the CR patients had subsequent progression while 2 PR patients had progression 7 and 10 months after the end of therapy. The macrophage counts increased significantly in the BM after the first three months of therapy (P 〈 0.01; r2=0,8927). This was parallel to a significant increase in the microvessel counts (P 〈 0.05, r2= 0,1547). The within-group comparisons showed that both counts were always significantly correlated (P 〈 0.001). Regarding angiogenic plasma biomarkers, preliminary data of bFGF, VEGF and HGF concentrations showed a trend, albeit not significant, to decrease after the first three cycles of therapy. Most common Grade 3–4 adverse events were hematologic and included neutropenia (48%), thrombocytopenia (18%) and anemia (6%). Other events included 4 patients (12%) with Grade 3–4 neutropenic fever and 3 patients (9%) with Grade 3 bacterial pneumonia. Grade 3–4 hypotension and dyspnea developed in 1 and 3 patients respectively; no patient developed thrombo-embolic or neuropathic complications. Conclusions Results from this study confirm the high therapeutic activity of Len in association with Dex in patients with relapsed and refractory MCL with a favourable safety profile. The significant increase of the macrophage infiltration in the BM seems to be a possible immunomodulatory effect of Len. Perhaps, the increase in microvessel counts may be induced by the activated macrophages and be an example of “indirect angiogenesis”. On the other hand, angiogenic plasma biomarkers tend to be lower, suggesting only a limited effect of Len on the neovascularization. Disclosures: Off Label Use: Lenalidomide in Mantle Cell Lymphoma. Vitolo:Celgene: Membership on an entity's Board of Directors or advisory committees.

Description: Introduction: Accordingto National Comprehensive Cancer Network (NCCN) and ESMO guidelines on Waldenstrom’s Macroglobulinemia (WM) bendamustine may be considered as a therapeutic option in first line treatment or in relapsed refractory disease. Even though there are only two clinical trials including a limited number of patients addressing the role of bendamustine and rituximab (BR) treatment in WM. Patients and Methods: To define the efficacy and tolerability of BR combination as salvage regimen in WM patients, we retrospectively analyzed the outcome of symptomatic refractory relapsed patients treated with BR in 14 Italian centres. All patients receiving at least one day of treatment were included in the study. Treatment consisted of: R 375 mg/sqm iv day 1 and B iv days 1, 2. Therapy was administered every 4 weeks up to 6 courses. Results: Seventy-one patients are included in the study. As regards B dosage; 45 patients (63%) received the highest dose of 90 mg/sqm while 22 (31%) were treated with 70 mg/sqm. The 4 patients (6%) with a cumulative illness rating scale ≥ 6, received the lowest dose of 50 mg/sqm. At treatment, median age was 72 years (49-88), sex ratio M/F 46/25. Mediannumber of prior regimens was 2 (range 1-6). Twenty-four patients (34%) presented with refractory disease. The majority (90%) of patients had been previously treated with alkylating agents, 30% had also received purine analogues based treatments. Previous R was administered in the 77% of cases. The main reason (62%) for starting treatment was anemia followed by adenopathy and/or splenomegaly (35%). Median IgM level at treatment was 3815 mg/dL.Overall 361 courses of BR treatment were administered, median number 6 (range 1-6) with 47 (66%) of patients completing the 6 planned courses. Toxicity was discontinuation cause in 10 patients (14%): 4 infection, 1 fatal, 6 myelosuppression. In the remaining 14 treatment was discontinued for clinical clinical decision after disease reassessment. No difference in terms of treatment discontinuation was observed according to B dosage and age. Overall response rate (ORR) was 80.3% including: 7% complete remissions (CR), 15.5 % very good partial remissions (VGPR), 52.2% partial remissions (PR) and 5.6% of minor responses. A stable disease was observed in 16.9% of patients. One (1.4%) disease progression and one death were recorded. A progressive decrease of IgM level was observed during follow-up leading to an amelioration of response in 4 cases leading to a final ORR of 84.5%. None of the clinical and biological characteristics considered (age, sex, disease status, previous lines of treatment, previous fludarabine, bulky disease, Hb and IgM level, beta 2 microglobulin, B dosage) had an impact on ORR achievement. A better quality of response (CR plus VGPR) was observed in patients with an IgM level 〈 3000 mg/dL and in those treated with the higher dosage of B (90 mg/sqm). After a median follow-up of 19 months (3-54) 11 of the 57 responding patients met the criteria for disease progression. No difference was observed when patients were stratified according to the quality of response. B dosage did not impact disease progression. Considering that most of the patients received prophylactic growth factors, grade 3-4 neutropenia developed in only 13% of courses, 36% of patients. Dose modification or delayed treatment administration was necessary in 4 and 10% of courses respectively. During treatment we recorded 14 episodes of FUO and 5 major infections, leading death in one case. After a median follow up of 19 months none of the patients developed secondary myelodisplastic syndrome, acute leukemia or diffuse large B-cell lymphoma. In 3 cases a solid cancer was observed. Conclusion: BR combination showed to be as effective as more intensive salvage regimens in pretreated WM patients. Treatment showed to be well tolerated even in elderly patients with limited episodes of myelosuppression and infections when compared to purine analogues including regimens. Disclosures No relevant conflicts of interest to declare.

Description: High dose (HD) chemotherapy followed by peripheral blood stem cell (PBSC) is widely used in the management of hematological malignancies and chemosensitive solid tumors. Different strategies of PBSC mobilization have been described, but currently the standard approach has not been established. Satisfactory results have been obtained by different chemotherapy schedules followed by haemopoietic growth factors: particularly HD Cyclophosphamyde or HDAra-C have a well known high mobilizing activity. With the intention to minimize hematological toxicity due to HD chemotherapy we performed this study to evaluate the mobilizing efficacy of intermediate dose Ara-C (IDAra-C). Methods: Pts with haematological malignancies received as mobilization treatment Ara-C 800 mg/m2 every 12 h for 6 doses followed by G-CSF 300 μg/d starting day +3 from the end of treatment until completion of leukapheresys (LP). CD34+ cells count was performed from day + 9. Failure of mobilization was defined as a persistent CD34+ cells count 10/μL CD34+ underwent LP. Pts not reaching the target of 2.5 x 106/kg CD34+ were considered as low mobilizer. Results: 98 pts, median age 56 y (range 27–70), underwent priming with IDAra-C. Disease characteristics are listed in table 1. All but 5 pts presented bone marrow involvement at diagnosis. Sixty-nine pts had previously received fludarabine, 56 anthracyclines and 30 alkilating agents. Thirty-three of the 98 pts had been considered low mobilizer or had failed a previous mobilization attempt, with HDAra-C in 20 cases A successful mobilization (threshold level 〉2.5 x 106/kg CD34+) was obtained in 73 pts (74,5%) (9/14 NHL, 42/43 CLL, 6/7 MM, 16/34 AML) with a median collection of 12,34 x 106/kg CD34+ (range 2,57–76,5). The peak value of CD34+ cells in the peripheral blood was achieved after a median of 13 d (range 10–19) from the end of therapy and a median of 1 LP (range 1–3) was required for a target collection. An adequate harvest was also observed among 17 of the 33 (51.5%) pts failing a previous mobilization attempt. After IDAra-C the median time to reach PMN 〉1000/μL and PLT 〉50000/μL was of 6 and 8 days respectively. There were no treatment-related deaths. During neutropenia we recorded 25 episodes of FUO, 9 infections microbiologically documented and 2 infections clinically documented. Median days temperature 〉 38°C was 2 (range 1–6). Extraematological toxicity consisted of: 1 gastrointestinal bleeding WHO III and 1 episode of atrial fibrillation. Overall 39 pts have been transplanted so far; median days for PMN 〉500/μL and PLT 〉50000/μL engraftment was of 9 and 12 d respectively. In conclusion IDAra-C and sequential G-CSF allowed predictable and efficient PBSC harvest in a limited number of leukapheresis session. Hematological recovery was rapid and toxicity manageable. These data confirm, in a larger series, the high mobilization activity of IDAra-C in CLL as previously reported. Moreover satisfactory efficacy has been observed in pts failing previous mobilization attempt with alternative regimen. This approach should be considered as an effective way to exploit a known mobilizing activity of Ara-C minimizing toxicity. Table 1 Disease characteristics AML NHL CLL MM ToT CR 32 3 35 3 73 CR 〉 1 2 3 − − 5 PR − 2 − 2 4 nPR − − 6 − 6 SD − 1 1 2 4 PD/RELAPSE − 5 1 − 6 Tot 34 14 43 7 98 median time from last treatment (months) 2,0 2,3 4,3 2,6 3,4

Description: Abstract 1713 Poster Board I-739 Introduction: Previous reports have highlighted the activity of Lenalidomide (Len) in patients with relapsed or refractory mantle cell lymphoma (MCL), achieving a 53% overall response rate (ORR), which included 20% complete responses (CR) (Haberman et al. Br J Haematol. 2009). In vitro studies on Burkitt's Lymphoma and MCL cell lines showed that combining Dexamethasone (Dex) with Len results in potent and synergistic anti-proliferative effects. To assess whether this effect translates to a clinical setting, and on the basis of data coming from multiple myeloma, we initiated a prospective, multicenter, phase II study, to evaluate safety and efficacy of Len administered in combination with Dex for adult patients with relapsed or refractory MCL. Methods: Patients had to have ≥1 prior treatment regimen, and were either not eligible for, or had relapsed after, more intensive treatments including stem cell transplantation (SCT). During the induction phase (month 1 to 3), patients received Len 25 mg/day on days 1 to 21 and Dex 40 mg/day on days 1, 8, 15, 22 of a 28-day cycle (Len Dex). Enoxiparin 4.000 U/day was administered as anti-thrombotic prophylaxis. Patients who achieved a partial response (PR) or stable disease (SD) at the end of the induction phase continued to the consolidation phase, which consisted of treatment with Len Dex until disease progression, unacceptable toxicity, or a CR, for a maximum of 12 months. Patients with a CR at the end of the induction phase, or those who achieved a CR during consolidation, received an additional 3 courses of Len Dex. The primary objective is to evaluate the ORR and CRR (IWG criteria Cheson et al 2007). Secondary objectives include safety, response duration (RD), overall survival (OS), and to explore changes in tumour biomarkers relative to response to treatment with Len Dex. Severity of adverse events (AE) is graded on a scale of 1 to 5 (NCI CTCAE v.3). Results: Between July 2008 and July 2009, 33 patients were enrolled on this study, representing the intent to treat population. Patients' median age is 68 years (range 51-80); 30 have the classic histology while 3 patients have the blastoid variant; 9 patients previously received two lines of therapy, 9 patients had three lines and 12 patients had 〉3 prior lines (median 3; range 1-7). Twelve patients previously underwent an autologous SCT and 7 received prior therapy with Bortezomib. At present, 21 out 33 enrolled patients are evaluable for response to the induction phase of the study: 11 patients responded to Len Dex (52% OR), including 3 CRs (14%); 1 patient (5%) has SD and 9 patients (43%) either had not responded or had progressed while on study. Nine patients discontinued treatment for the following reasons: skin reaction in 1 patient, progression in 7 patients, 1 patient died while on study. So far, 28 patients are valuable for safety during the induction phase. Most common Grade 3-4 adverse events were hematologic and included leucopenia (n=6; 21%), neutropenia (n=10; 36%), thrombocytopenia (n=4; 14%) and anemia (n=1; 3%). Other events included 3 patients (10%) with grade 3-4 neutropenic fever and 2 patients (7%) with grade 3 bacterial pneumonia. Grade 3-4 hypotension and dyspnea developed in 1 patient each, and none of the patients developed thromboembolic or neuropathic complications. Initial results from this study confirm the high therapeutic activity of Len in patients with relapsed and refractory MCL. Conclusions: Preliminary evaluation of the safety and efficacy of the Len Dex regimen indicates that the combination has a favourable safety profile, but the addition of Dex does not appear to substantially improve the activity of Len in the treatment of patients with relapsed or refractory MCL. Disclosures: Off Label Use: Lenalidomide is off label for treatment of Non Hodgkin Lymphoma.. Vitolo:Celgene: Lecture fees.