Abstract: Introduction. Observational studies from patients treated outside controlled clinical trials offer real life information and are relevant to understand whether data derived from prospective trials are reproducible in the clinical practice. A retrospective observational study was carried out by the GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) group in order to evaluate the clinical characteristics and outcome of patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib in Italy within a Named Patient Program (NPP). The NPP was intended to offer free and early drug access to CLL patients until ibrutinib became available on the Italian market. Methods. Patients included in the NPP program had refractory or relapsed (R/R) disease with progression within 24 months after prior chemo-immunotherapy, and/or 17p deletion/TP53 mutations. Patients were also required to have an ECOG performance status ≤2; serum creatinine ≤2 times, liver enzymes ≤3 times and total bilirubin ≤1.5 times the upper limit of normal. Key exclusion criteria were: the need of a concomitant treatment with a strong CYP3A inhibitor or warfarin, an allogeneic stem cell transplantation within the past 6 months or an ongoing active infection. All patients included in the program received ibrutinib orally as a single agent at the standard dose of 420 mg daily. Clinical data of 110 patients included in the NPP program between January 2014 and November 2014 have so far been collected and analyzed using the Research Electronic Data Capture (REDCap) system. Patients were managed at 20 Italian centers and received at least one dose of ibrutinib. Clinical data were reported by the treating physicians. Results. The median age of patients was 69.9 years (range 49.8-83.3); 53% were in Rai stage III-IV, 32% in stage II and 15% in stage 0-I. Sixty-two percent of patients had relapsed disease, 38% were refractory to prior treatment. The presence of a 17p deletion and/or TP53 mutations was recorded in 51 R/R patients. Eighty-six percent of patients had an unmutated IGHV gene profile. The median number of prior treatments was 3 and included allogeneic stem cell transplantation in 4 cases. Two or more comorbidities were reported in 57 patients (52%) and included atrial fibrillation (AF) in 10 (9.1%) and hypertension in 40 (36.4%). After a median follow-up of 12.1 months (range, 1.6-24.6), 87 patients (79%) were still on ibrutinib. A response to ibrutinib was reported in 98/110 patients (89.1%). The best recorded response was a CR/CRi in 19 patients (17.3%), while a PR was reported in 79 patients (72%; PR-L 21.1%). Similar response rates were observed in patients with unmutated IGHV genes (91.9%) and in those with 17p deletion/TP53 mutations (90.3%). At 12 months, the progression-free survival (PFS) and overall survival (OS) were 92.9% (95%CI: 87.9-98.2) and 95.2% (95%CI: 91.1-99.4), respectively. PFS at 12 months of patients who achieved a response was 96.3%, 98.9% in unmutated IGHV patients, 90.7% in those with 17p deletion/TP53 mutations. Five patients (4.5%) died during the NPP program (1 patient each for sepsis, heart failure, ileus perforation, cancer, unknown cause). Adverse events (AE) were recorded in 75 patients (68.2%); in 47 (42.7%) they were grade ≥3. Any grade AEs recorded in ≥5% of patients were: infections (35%; grade ≥3, 22%), granulocytopenia (18.8%; grade ≥3, 17.2%), bleeding (15.5%; grade ≥3, 2.7%), fever of unknown origin or febrile neutropenia (12%; grade ≥3, 5.4%), AF (10.9%; grade ≥3, 4.5%), diarrhoea (8.3; grade ≥3, 2%), hypertension (7.2%; grade ≥3, 5.4%). A new event of AF occurred in 1/10 patients with a prior history of AF. Warfarin was required in 1 patient with AF and this was the reason for ibrutinib discontinuation. Conclusions. The results of the first interim analysis of this retrospective, real life study confirms that ibrutinib, as a single agent, is an effective treatment for patients with poor-prognosis CLL. Our data also suggest that ibrutinib given to unselected patients, in a compassionate-use program, shows a clinical activity and a safety profile comparable to those reported in prospective trials. Data collection is ongoing in order to complete the analysis of this large NPP cohort in Italy. Disclosures Marasca: Roche: Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria. Coscia:Karyopharm: Research Funding; ROCHE: Honoraria, Other: Advisory board; Janssen: Honoraria; Gilead: Honoraria; Mundipharma: Honoraria. Zinzani:Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celegene: Membership on an entity's Board of Directors or advisory committees. Molica:Jansen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche Italy: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Speakers Bureau. Orlandi:Ariad: Honoraria; BMS: Honoraria; Novartis: Honoraria. Ghia:Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria; Adaptive Biotechnology: Consultancy; Roche: Honoraria, Research Funding. Foà:Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; BMS: Consultancy; Genentech: Consultancy; Pfizer: Speakers Bureau; Ariad: Speakers Bureau.

Abstract: Introduction: Postremission treatment in adult acute myeloid leukemia (AML) is mandatory to improve long-term remission duration. Allogeneic stem-cell transplantation (allo-SCT) is considered gold standard in younger patients (pts) with higher risk of relapse, whereas in pts categorized as standard-risk (SR) AML the optimal treatment remains an open issue. High-dose cytarabine (HD-ARAC) is considered the backbone of postremission treatment in SR AML. The optimal dose and schedule, and the clinical benefit of additional chemotherapeutic agents remain controversial (Schaich, 2011- Lowenberg, 2011- Lowenberg, 2013) as well as the relative efficacy of HD-ARAC in the different cytogenetic and molecular subgroups of SR AML. We analyzed the very long term outcome of consecutive unselected AML pts treated according to AML 00 NILG protocol (Bassan, Blood, 2003: 102; 11) with three repetitive HD-ARAC-based cycles, associated with idarubicin, followed by limited peripheral blood stem cell (PBSC) support, in order to reduce toxicities. Methods: We evaluated 263 consecutive AML pts, diagnosed at our Institution, from January 2001 to March 2016 (median age 52 years - range 15-65). The treatment plan included induction with ICE (Idarubicin-Cytarabine-Etoposide) followed by IC consolidation or HD-ARAC/HD-idarubicin (SPLIT therapy) in refractory cases. ARAC 1g/mq bd for 4 days (A8) was given to CR pts, to collect 3-6x10^6 CD34/kg in 3 aliquots. Patients with ELN favorable or intermediate risk AML, considered SR AML, received 3 cycles of HD-ARAC (2g/mq bd for 5 days) plus idarubicin (8mg/mq for 2 days) with PBSC reinfusion (1-2x10^6 CD34/Kg) (A20). The pts with insufficient CD34 cells yield, received 2 courses HD-ARAC (1g/mq bd for 5 days) plus idarubicin (10mg/mq day 1) (A10). The cumulative dose of ARAC and idarubicin given according to A20 protocol were 69,4 g/mq and 162 mg/mq, respectively. Results: Among 263 pts, 142 (54%) pts were considered SR and 116 (44.1%) HR. Only 5 pts were lacking molecular or cytogenetic information (1.9%) to allow ELN risk classification. Accordingly, 65 pts (25.2%) were favorable [35.4% core binding factor (CBF) positive, 9.2% CEPBA mutated and 55.4% NPM mutated], 87 (33.7%) Intermediate-I, 45 (17.4%) Intermediate II and 61 (23.7%) adverse risk. CR rate after ICE treatment was 77.6% (204/263), 95.8% in SR and 56% in HR pts and after ICE+SPLIT it was 88.2% (232/263); early or aplastic death was 6%. A8 course was administered in 218 pts, of whom 179 were successfully mobilized (82.1%). Among 136 SR pts, 127 were received HD-ARAC (A20 or A10), 4 allo-SCT for early relapse, 3 pts did not proceed to A20 because of prolonged cytopenia and 2 are ongoing. Hematological toxicity was acceptable. ANC recovered at a median of 10 days after CD34+ cells reinfusion. Two death in CR occurred within 100 days after A20 therapy (1.6%). After a median follow-up of 53.3 months (range 1-172), the median survival of SR AML patients was 118.9 months, the DFS and OS at 5 y were 51+/-4.8% and 56.5+/-4.7%, and at 10 y 43.3+/- 5.9% and 49.6+/-5.7%, respectively. According to ELN risk, the OS at 5 y and 10 y was 78.3+/-6% and 68+/-8.7% in favorable (median OS not reached), 52.3+/-8% and 46+/-9.4% in Intermediate-I (median OS 118.8 months), and 42+10% and 33.6+/-10.9% in Intermediate-II (median OS 33.1 months) (p0.0034) (Figure1). According to molecular characteristics, the OS at 5-y was 100% in CEBPA-mutated, 77+/-9% (+/-SE) in CBF-mutated and 71+/-11% in NPM-mutated subgroups, respectively (Figure 2). In NPM-mutated pts it was 56+/-14% if FLT3 was mutated and 75+/-10% if not. At 8-y OS was not evaluable in CEBPA-mutated, it remained 77+/-9% in CBF mutated but dropped to 47+/-15% in NPM-mutated pts due to late relapses (28%), which occurred in pts without FLT3. The median time to relapse in NPM pts was 17 m, the latest relapse occurred after 97 months. Conclusion: A postremission program with repeated courses of HD-ARAC associated to idarubicin and limited autologous CD34+ cells support was feasible, well tolerated and very effective, also long-term, in pts with ELN favourable or intermediate risk AML. The late relapse tendency of NPM-mutated AML is puzzling and should be considered by innovative programs aimed at improving these results. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Abstract: Introduction: Advanced stage follicular lymphoma (FL) is generally considered incurable. Although multiple remissions after treatment are possible, relapse is considered the rule, and the time to progression tends to become shorter after each relapse (Johnson, JCO 1995). Over the last decades, after the introduction of monoclonal anti-CD20 antibodies and of better treatment programs, the prognosis of FL has markedly improved from a median OS of 7 years to a 10-year OS rate 〉 80%. Moreover, clinical observations of patients (pts) experiencing very long progression-free periods despite more than one previous treatment failure, have become not rare, suggesting that some pts could achieve operational FL cure. To assess the frequency of those prolonged long-term remissions and search for potential predictive factors, we have retrospectively analyzed the consecutive series of pts with FL seen at our institution. Methods: FL pts, aged 〉 18 years, in maintained remission for more than 5 years after at least two lines of treatment were selected as "potentially cured" FL (PC-FL) and analyzed in detail. Their main characteristics at diagnosis and at last relapse, the different lines of treatment received and the time intervals (time to next treatment: TTNT) between them, were recorded and compared with those of FL pts seen in the same period (control group). Treatment strategies used were grouped and defined as follows: radiotherapy or surgery, for stage I-II (local), anthracycline and/or alkylating agents regimens (Alk/Ant), purine analogues regimens (Pur), monoclonal antibodies/radioimmunoconjugates as single agent (MoAb), autologous transplantation (ASCT). Results and discussion: Among 385 consecutive FL pts seen from January 1987 to December 2011, 56 (14,5%) met criteria for PC-FL. Their clinicopathological features at diagnosis, compared to controls, are shown in Table I. There were no significant differences except for a younger age (51 vs 58 years, p 〈 0.00016) and for a lower frequency of grade 3a histology (p=0.04) in PC-FL pts. First line treatment used did also not differ (p=0.29). Among PC-FL pts, 33 received two, 16 received 3 and 7 more than 3 treatment lines. The median duration of last complete remission was 118+ months, whereas the median duration of the remission preceding the last treatment had been 24 months; disease duration from diagnosis to the last relapse preceding long term remission had been 50,5 months. The last treatments received before long-term remission were variable including local in 10 (18%), Alk/Ant in 5 (9%), Pur in 11 (19%), MoAb in 10 (18%) and ASCT in 20 (36%). Pts characteristics at last relapse and remission duration were similar among different treatment subgroups, except that more pts in localized stage received local treatments. Comparing clinicopathological characteristics of PC-FL pts at diagnosis and at last relapse there were no differences except for FLIPI score, which was significantly lower at relapse (low FLIPI 34% at diagnosis, 68% at relapse, p=0.002). First-line and last treatments were similar except that more pts underwent ASCT as last treatment, as expected since frontline ASCT is not recommended. In 10 pts TTNT after first-line was longer than 5 years and 7 of them are still in prolonged remission (median 11+ years) after second-line treatment, representing a particularly favorable subgroup. In 26 (46%) of PC-FL pts TTNT was shorter than 24 months after first line therapy. Among 14 of them who received R-chemo at diagnosis (POD24, Casulo, JCO 2015), 8 (57%) obtained long remission after ASCT, given in second line in six. Conversely, ASCT was used in only 1 of 12 pts not receiving Rituximab at diagnosis. Conclusions: Approximately 15% of FL pts could currently achieve a very prolonged remission of about 10 years, even after multiple relapses. Its duration was 5x that of the last treatment line and more than twice that of active lymphoma, strongly suggesting the possibility of having achieved lymphoma cure. Younger age and grade 1-2 FL histology at diagnosis, and FLIPI low risk at relapse favored the achievement of PC-FL status. No specific treatment was associated with PC-FL and even an early relapse after first line treatment did not preclude to reach PC-FL, although early ASCT may be more effective for POD24 patients. Whether the achievement of PC-FL status may be related to biological factors will be interesting to be investigated in the next future. Disclosures Rossi: Roche: Membership on an entity's Board of Directors or advisory committees; 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; Teva: 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; Novartis: Honoraria; Mundipharma: Honoraria; BMS: Honoraria; Sandoz: Honoraria.

Abstract: Introduction: XPO1 (CRM1, Exportin 1) is the sole transporter of many tumor suppressor proteins (including MYC, BCL2, BCL6, BTK, IkB) and is elevated in non-Hodgkin Lymphoma. Selinexor (Sel, KPT-330) is an oral covalent inhibitor of XPO1, the first clinical molecule of the Selective Inhibitors of Nuclear Export drug class. The phase I clinical trial of Sel in hematologic malignancies showed promising early single-agent efficacy with modest toxicity in relapsed Diffuse Large B-cell Lymphoma (DLBCL, Gutierrez et al, ASCO 2014). DLBCL, the most common lymphoid malignancy, is currently cured in only 10% of relapsed patients, and consists of 2 subtypes based on putative cell of origin (COO): activated B-cell (ABC) and germinal center B-cell (GCB). We performed preclinical studies of Sel, modeling its single-agent efficacy in frontline and relapsed DLBCL and its potential synergy with other clinically relevant therapeutics. Long-term follow-up data on patients(pts) treated with Radiolabeled antibody 90-yttrium-Ibritumomab Tiuxetan (RIT) are necessary to define the role of RIT-therapy (RIT-t) in current clinical practice. There are few reports about the use of RIT outside clinical trials. Outcome and toxicity of radioimmunotherapy remain a matter of concern. Incidence of MDS/AML reported after RIT-t as consolidation in front line varies from 3 to 4.3% (Czuczman et al, JCO 2007; Morschhauser et al, JCO 2012). A recent study with RIT and autologous stem cell transplantation (ASCT) as front line therapy in mantle cell lymphoma reported 20% incidence of secondary malignancies, (Arranz et al, Haemat 2013). So the aim of this study was to analyze the outcome of pts treated with RIT-t in clinical practice and to assess the incidence of secondary neoplasia particularly MDS/AML. We included in this retrospective analysis all pts with Diffuse B Large Cell Lymphoma (DBLCL), Follicular Lymphoma (FL) and Marginal Zone lymphoma (MZL), treated with RIT-t over the last decade at our Institution. We adopted the standard RIT therapeutic regimen: infusion of 250 mg/m2 rituximab on day 1, a second 250 mg/m2 dose on day 7, followed by dose of RIT (0.4 mCi/kg), administered 4 h following rituximab infusion. Response assessment was made as recommended by International Workshop criteria. Survival analysis was performed with Kaplan-Meier method and univariate analysis with Log-Rank test with a significance at 0.05. Between March 2006 and January 2014 61 pts underwent RIT-t, of these 57 had complete data and were considered for analysis. There were 16 DBLCL, 29 Follicular Lymphoma and 12 MZL. Twentythree were male, 34 female. Median age at diagnosis was 62 years(yrs) (range 36; 79), 66yrs (range 39;79) at RIT-t. Thirteen pts (all DBLCL) received RIT-t as front line consolidation. Forty-four pts (3 DBLCL, 12 MZL, 29 FL) underwent RIT-t after ≥1 therapy line: one prior line was received by 15pts, 2 by 19, 3 by 8 and 4 by 2. Before RIT-t 24pts were in relapse (2DBLCL, 2MZL, 20FL), 9 were refractory (2 MZL, 7 FL), 7 in partial response (1 DBLCL, 5 MZL, 1FL) while 4 were in complete remission (2 MZL, 2FL). Disclosures No relevant conflicts of interest to declare.

Abstract: BACKGROUND: Median age of patients (pts) with acute myeloid leukemia (AML) ranges between 69 and 72 years in population-based series (SEER, 2012; Juliusson, 2009). The prognosis of elderly AML is exceedingly poor with overall 2-year survival of 10% (Juliusson, 2011). The use of intensive chemotherapy (i-CT) in elderly AML patients as opposed to non-intensive chemotherapy (ni-CT) or best supportive care (BSC) is still debated. Age is still the major driver of treatment choice but, in recent years, the role of pts' fitness and comorbidities was underscored. In 2013, a panel of experts proposed a set of objective criteria to define pts fit or unfit to conventional i-CT, ni-CT or BSC (Ferrara et al, Leukemia, 2013). Since such criteria derived from experts opinion, they need to be validated in the clinical setting to become an useful tool for therapy decision making. AIMS: Fitness criteria were retrospectively applied to a population-based series of pts with AML (no M3), to evaluate a) their actual applicability; b) the concordance between fitness categorization of pts and the type of treatment they actually received; c) the outcome of pts according to fitness, to the prognostic stratification of European Leukemianet (ELN) and to the treatment received. PATIENTS and METHODS. We evaluated 362 pts aged 〉 65 y, diagnosed at five Hematology Centres of the Hematological Network of Lombardy in Northern Italy (REL). Pts were diagnosed between January 2008 and May 2014. Their median age was 73 y (range 65-94 y). Their categorization according to fitness criteria was carried out retrospectively by the teams of physicians who had followed pts and through medical files. Pts were classified as fit to i-CT (FIT), unfit to i-CT (UNFIT), or unfit even to ni-CT (FRAIL). According to ELN prognostic criteria, applied in 201 de novo AML, pts were at low-risk (36 pts: 18%), of which 7 (3,4%) with CBF leukemia, intermediate-I (75 pts: 37%), intermediate-II (30 pts: 15%), or high risk (60 pts: 30%). Criteria were not applicable in 34 pts (14%) lacking karyotype or molecular data. The group of 127 pts (35%) with AML therapy-related or secondary to myeloid neoplasms was considered at high clinical risk (cHR). According to physicians decision, 139 pts (38.4%) had received i-CT, 65 pts (18%) ni-CT, including low-dose arac, azacytidine or experimental non-myelotoxic drugs, and 158 pts (43.6%) BSC. RESULTS. Fitness criteria were not applicable in 12 pts (3%), because of insufficient data. Among 350 evaluable pts (97%), 170 (46.9%) were FIT, 140 (38.7%) were UNFIT, and 40 (11%) were FRAIL. Their median age was 69, 79 and 75 years, respectively (p 〈 0.0001). Median overall survival (OS) of FIT, UNFIT and FRAIL pts was 12.5, 3.7 and 1.8 months, respectively (FIT vs others: P=0.0001, UNFIT vs FRAIL: p=0.049) (Figure 1). Overall concordance between fitness criteria and the treatment actually received by pts was 80% (71% in FIT, 88% in UNFIT and 90% in FRAIL pts). Median OS of pts receiving i-CT, ni-CT or BSC was 14.7, 14.2 and 4.2 months in FIT, (p 〈 0.0001), 8.6, 8.9, 2 months in UNFIT (p 〈 0.0001) (i-CT vs ni-CT: P:NS), respectively. Median OS inFRAIL pts receiving ni-CT (4 pts only) or BSC was 11.5 and 2 months, respectively (p:NS). Considering pts receiving i-CT, their outcome was significantly related both to ELN/clinical risk and to fitness. CR rate was 96.5% in LR, 66% in Int-I, 54% in Int-II, 46% in HR, 53% in cHR (p=0.0013). OS at 2y was 40% in LR/Int-I vs 25% in Int-II/HR/cHR pts (P=0.04). Median OS was 14.7 in FIT vs 8.6 months in UNFIT/FRAIL pts (P=0.022). By integrating ELN prognostic stratification with fitness, the use of i-CT obtained a significantly better median OS of 20 months in FIT pts at ELN LR/Int-I compared to 8,5 months in pts at Int-II/HR/cHR (p 0.014) (Figure 2). CONCLUSIONS. The fitness criteria proposed were easily applicable even retrospectively and in a multicenter setting. Fitness was significantly related to patient's survival. In FIT and UNFIT pts outcome was similar with either i-CT or ni-CT, but these results need to be tested prospectively on larger cohorts. Integrating fitness with ELN criteria identifies a subgroup of FIT pts at low/Int-I ELN risk with a CR rate of 76.6% and a median OS of 20 months when treated with i-CT. Therefore fitness criteria seem to be a good tool to identify pts who can benefit from i-CT or ni-CT in alternative to BSC and to assist in the decision to use i-CT in elderly AML patients. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Abstract: The efficacy of posaconazole prophylaxis against invasive fungal infection (IFI) in acute myeloid leukemia (AML) patients during induction therapy has been demonstrated both in randomized and real-life studies. Absorption of posaconazole is enhanced by food intake, which may be impaired by gastrointestinal mucositis. However, correlation between posaconazole serum levels and breakthrough IFI has not been clearly demonstrated and the usefulness of therapeutic drug monitoring (TDM) is still a matter of debate. Aims In order to clarify the role of posaconazole TDM in preventing opportunistic infections, we correlated posaconazole serum levels with the incidence of breakthrough proven/probable IFI and the need for empiric/pre-emptive/targeted antifungal therapy among AML induction patients. A comparative analysis with an historical cohort receiving mainly itraconazole prophylaxis was also performed. Patients and Methods Since June 2004 a program of active epidemiological surveillance is ongoing at our Institute. Posaconazole prophylaxis was routinely introduced among AML induction patients on July 2011; data concerning incidence of IFI during AML induction were extracted from two consecutive periods (Jul2009-Jun2011 and Jul2011-Jun2013). Patients received posaconazole at 200 mg three times a day; 1st serum posaconazole level was determined on day 7 and repeated every 7 days. A serum level ≥500 ng/mL was considered adequate. Serum galactomannan (GM) was monitored two times a week; thorax CT scan was performed within 3 days from the onset of fever. Systemic antifungal therapy was started empirically, in the case of persistent fever, with or without radiological signs of fungal infections. Results Overall, 120 AML patients were evaluated, 60 in both periods. The two cohorts did not differ in median age, M/F ratio and type of treatment. During the 1st period 9/60 (15%) breakthrough IFI (2 candidemia, 7 aspergillosis) were observed, as compared to 2/60 (3.3%) in the 2nd period (1 candidemia and 1 aspergillosis), p=0.027 (Chi-square test). In all but one cases of aspergillosis, GM positivity was the microbiological criterion to meet the diagnosis of probable/proven IFI. The need for systemic antifungal therapy was similar in both periods (40% and 38.3%, respectively). Posaconazole serum levels was available in 50/60 patients (83%) during the 2nd period. Mean serum concentration did not change significantly over time (mean value±SE: 551±48.7 543±64, 643±107.4, 698±164.7 at 1st, 2nd, 3rd, 4th week of therapy respectively, p=0.64). Adequate serum levels throughout the induction period were maintained in 19 cases (38%). None of them developed IFI. Posaconazole serum level was below the therapeutic threshold in the patient developing candidemia and not evaluable in the one who developed pulmonary aspergillosis 3 days after starting posaconazole prophylaxis. Systemic antifungal therapy, was given to 4/19 (21.1%) patients with persistently adequate posaconazole serum levels as compared to 13/31 (41.3%) patients with at least 1 posaconazole serum level below the therapeutic threshold (p=0.13). Conclusions Our study confirms that posaconazole prophylaxis significantly reduces the incidence of proven/probable breakthrough IFI, particularly aspergillosis, in a “real life” setting. No patient with persistently adequate posaconazole serum levels developed IFI. In this subgroup the need for systemic antifungal therapy was halved compared to patients with below-target posaconazole serum levels. Weather the reduced sensitivity of diagnostic biomarker tests due to azole prophylaxis may contribute to underestimate a diagnosis of IFI remains an open question. Disclosures: No relevant conflicts of interest to declare.