ALBERT

Description: Background Thrombotic episodes are the major complication in the follow-up of Philadelphia negative Myeloproliferative Neoplasms (MPN), with high morbidity and mortality, as reported in several retrospective studies. At present, however, few prospective data are available on the early incidence of these complications. Methods To address this issue, we report on 1087 patients [M/F 508/579, median age 67.6 years, interquartile range (IQR) 55.2 - 75.9] with newly diagnosed MPN enrolled in the prospective database of our regional cooperative group since January 2011. Of them, 571 (52.5%) had Essential Thrombocythemia (ET), 303 (27.9%) Polycythemia Vera (PV) and 213 (19.6%) Primary Myelofibrosis (PMF). The main clinical features at diagnosis of the whole cohort and according to the different MPNs are reported in the Table 1. Results On the whole, 22 episodes of thrombotic complications were reported in 1087 patients (2.0%) at a median interval from diagnosis of 18.2 months (IQR 7.4 - 29.7): in particular, 15 (68.1%) were arterial (8 cerebral, 2 coronaric, 4 in the lower limbs, 1 splancnic) and 7 (31.9%) venous (5 in the lower limbs and 2 in the upper limbs). As to the incidence of early thrombosis in the different MPNs, they were 13/571 (2.2%) in ET patients, 5/303 (1.6%) in PV patients and 4/213 (1.8%) in PMF patients (p=0.810): median time from diagnosis to thrombotic event was also similar in the 3 MPNs (p=0.311). The 4-year cumulative Thrombosis-Free Survival (TFS) of the whole cohort was 97.3% (95%CI 96.0 - 98.6): there was no difference among the 3 MPNs as to 4-year TFS [96.7% (95%CI 94.8 - 98.6) in ET, 97.8% (95%CI 95.9 - 99.7) in PV and 98.7% (95%CI 96.9 - 100) in PMF, respectively, p=0.668). Several clinical features at diagnosis (age, gender, Hb levels, WBC and PLT counts, spleen enlargement, JAK-2 V617F mutation and previous thrombotic events) were evaluated for a role in predicting thrombotic events: only age (p=0.009) and previous thrombotic events (p=0.009) were significant. Conclusions The incidence of early thrombosis seems low in the first 4 years after diagnosis of MPN based on our prospective database, without any difference among ET, PV and PMF: it is worth of note that only age and previous thrombotic events had a predictive role, thus confirming many retrospective reported data and reinforcing the prognostic value of old scoring system for thrombotic risk in MPN. Table 1 Table 1. Disclosures Breccia: Ariad: Honoraria; Pfizer: Honoraria; Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria. Latagliata:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Janssen: Consultancy, Honoraria; Shire: Honoraria.

Description: Thrombotic events are major complications in patients (pts) affected by Essential Thrombocytemia (ET) and Polycytemia Vera (PV). To compare thrombotic risk in these 2 groups, we evaluated retrospectively our database of 1249 ET and 623 PV pts diagnosed and followed in 11 hematological centers in the Latium region between 1/1980 and 12/2010: the diagnosis was done according to PVSG, WHO 2001 and 2008criteria based on the time of first observation. Baseline features of ET pts: 797F/452M,median age 62.9 yrs (range 19-96),median WBC count 8.8 x 109/L (range 1.2-57.7), median PLT count 812 x 109/L (range 457-3582), median Hb level 14.0 g/dl (range 6-20.5), JAK-2V617F positivity 59.7% with a median allele burden of 19,6% (range 0.2- 99.9), spleen enlargement in 18.7% of pts, previous thrombosis223/1239 evaluable pts (17.9%) [arterial 176/223 (14.1%), venous 47/223 (3.8%)]. Baseline features of PV pts: 289F/334M, median age 63.0yrs (range 21-91), median WBC count 10.1 x 109/L (range 3.5-37.6), median PLT count 457 x 109/L (range 169-1790), median Hb level 18.2 g/dl (range 10.5-24.8), JAK-2V617F positivity 94.3% with a median allele burden of 59.1% (range 0.3-99.9), spleen enlargement in 42% of patients, previous thrombosis 146/617 evaluable pts (23.7%)[arterial 114/617 (18.5%), venous 32/617 (5,2%)].in the ET cohort, after a median follow-up of 7.7 yrs, thrombotic complications were seen in 107/1141 evaluable pts (9.4%) [arterial60 (5.25%), venous 47 (4.11%)]; in the PV cohort, after a median follow-up of 8.5 yrs, thrombotic complications were seen in 107/623pts (17.2%) [arterial 67 (10.8%),venous 40 (6.4%)].All common risk factors for thrombosis were evaluated in multivariate analysis, searching the cut-off number for continuous variables with ROC curves. The significant variables at multivariate analysis for ET and PV pts are shown in the table; age, previous thromboses and spleen enlargement were risk factors in ET pts, while previous thromboses and JAK-2V617F allele burden were risk factors in PV pts. PLT count above ROC value seemed to be a protective factor in both cohorts. In conclusion, in contrast with the tendency to evaluate in a similar manner the thrombotic risk of PV and ET, data from our retrospective database showed that these 2 groups should be considered populations with different risk factors for thrombosis. Table 1.Putative prognostic factorsPolycythemia VeraEssential ThrombocythemiaHR95% C.I.pHR95% C.I .pPrevious thromboses2,311,13 - 4,740,021,871,08 -3,230,026Age ≥ 60 y1,540,79 - 2,990,211,901,18 - 3,060,009JAK2V617FPV: allelic burden ≥ 81% ET: pos1,951,03 - 3,710,040,760,48 - 1,210,25Plt countPV ≥ 452.109/L ET ≥ 944.109/L0,490,25 - 0,950,040,520,31 - 0,890,017Spleen enlargement0,670,34 -1,310,241,711,02 - 2,890,04CV risk factors (at least 1)0,920,41 - 2,030,830,870,51 - 1,490,62WBCPV ≥ 10,175.109/L ET ≥ 9,630.109/L1,090,57 - 2,080,801,410,89 -2,260,15 Disclosures No relevant conflicts of interest to declare.

Description: Dasatinib (DAS) has been licensed for first line treatment of patients (pts) with Chronic Myeloid Leukemia (CML): however, in the current clinical practice, DAS is often considered too toxic for the treatment of elderly CML patient. In particular, no data are available in very elderly CML pts as to toxicity and efficacy. To address this issue, we evaluated a "real-life" cohort of 39 CML pts in chronic phase aged 〉 75 years and treated with frontline DAS in 20 Italian Centers from 6/2012 to 10/2017. Main clinical features at diagnosis are reported in the Table 1. Overall, 23/39 pts (58.9%) had ≥ 2 comorbidities requiring concomitant therapies: according to ECOG scale, performance status at baseline was 0 - 1 in 34 pts (87.2%) and 2 in 5 pts (12.8%). Median interval from diagnosis to DAS therapy was 0.8 months (IQR 0.5 - 1.4). Daily DAS starting dose was 100 mg in 30 pts (76.9%), 80 mg in 1 pts (2.6%) and 50 mg in 8 pts (20.5%), respectively. All pts were evaluable for toxicity and efficacy; on the whole, grade 3/4 hematological and extra-hematological toxicities were detected in 6 (15.4%) and 11 (28.2%) pts, respectively. DAS therapy was permanently discontinued in 9 pts (23.0%) due to toxicity (3 pts in the first 12-month period of treatment and 6 beyond). Pleural effusions of all WHO grades occurred in 12 pts (30.7%) after a median period of DAS treatment of 16.3 months (IQR 2.2 - 31.8): in 4 of them pleural effusion occurred during the first 6-month period of treatment. Overall, 36/39 patients (92.3%) achieved at any time complete cytogenetic response (CCyR), 30/39 (76.9%) major molecular response (MR 3.0) and 16/39 (41.0%) deep molecular response (MR 4.0/4.5). Only 1 patient (2.6%) evolved in a blastic phase after 13 months from DAS initiation. After a median period of 27.8 months (IQR 19.1 - 37.5), 5 patients died (1 from blastic phase and 4 from unrelated causes): cumulative event-free survival and overall survival at 36 months were 63.2% (95%CI 45.2 - 81.2) and 85.3% (95%CI 73.3 - 97.3), respectively (Figures 1 and 2). In conclusion, these data indicate that DAS therapy may have a role also in the treatment of patients aged 〉 75 years, being effective as in younger subjects and having an acceptable safety profile. Disclosures Gugliotta: Novartis: Honoraria; Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria; Incyte: Honoraria. Abruzzese:Ariad: Consultancy; BMS: Consultancy; Novartis: Research Funding; Pfizer: Consultancy. Breccia:Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria; Incyte: Honoraria.