ALBERT

Description: According to the World Health Organization (WHO) 2008/2016 criteria for classification of myeloid neoplasms, a platelet (PLT) count ≥ 450X109/l, thus reduced from the previous WHO 2001 level ≥ 600 x 109/l, was considered the new PLT threshold for the diagnosis of Essential Thrombocythemia (ET). Aim of the study was to validate in a setting of current clinical practice this important diagnostic change and compare clinical and hematological features at diagnosis and during follow-up of patients with PLT ≥600 x 109/l versus patients with PLT 〈 600 x 109/l. We retrospectively analyzed data from 264 patients with ET according to WHO 2008/2016 criteria, enrolled in our center from 1/2008 to 12/2017. Patients were divided into Group A (G-A) (PLT ≥600 x 109/l at diagnosis) (199 patients - 75.4%) and Group B (G-B) (PLT ≥ 450 x 109/l 〈 600 x 109/l at diagnosis) (65 patients - 24.6%) and compared for clinical features at the onset, clinical course and follow-up. Main features and commonly recognized pro-thrombotic risk factors at diagnosis of the entire cohort as well as of G-A and G-B are reported in the Table 1. Among clinical features, only the median value of leukocytes was significantly higher in G- A [9.1 x 109/l, interquartile range (IQR) 7.8-10.3 vs 7.4 x 109/l, IQR 6.0-9.6; p = 0.001]. Among pro-thrombotic risk factors, only the median cholesterol value was significantly lower in the G-A [187 mg/dl (IQR 164-220) vs 204 mg/dl (RIQ 177-238); p = 0.048]. Cytostatic treatment was administered in 175 patients (71.1%) of entire cohort at different intervals from diagnosis, with a significantly higher rate in patients of G-A (76.9% versus 49.2%, p 1.000 x 109/l, highlights how thrombotic risk is unrelated to PLT value and leads to consider the administration of adequate cytostatic therapy even in patients with relatively lower PLT count at diagnosis. Disclosures Breccia: Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; BMS: Honoraria. Foà:INCYTE: Other: ADVISORY BOARD; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; GILEAD: Speakers Bureau; CELTRION: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; ROCHE: Other: ADVISORY BOARD, Speakers Bureau; NOVARTIS: Speakers Bureau.

Description: Abstract 5062 Thrombotic events occurring before or at diagnosis of Essential Thrombocythemia (ET) are a worldwide recognized prognostic factor for the incidence of thrombosis during the follow-up of ET patients: however, these previous thrombotic events have been considered on the whole in the vast majority of studies, without further characterization. Among 1063 ET patients collected in the retrospective database of the “Gruppo Laziale SMPC Ph-”, we revised 186 cases with a previous thrombosis and a known data of occurrence, to evaluate the role of the interval from previous thrombotic episode and the diagnosis of ET. In 95 patients (51. 1%) previous thrombotic event occurred 〈 24 months before diagnosis of ET (group A) while in 91 patients (48. 9%) thrombosis occurred ≥ 24 months before diagnosis of ET (group B). Clinical features of patients at diagnosis are shown in the Table: GROUP A GROUP B p Gender (M/F) 40/55 42/49 0.636 Median age (yrs) (Interquartile range) (IR) 64.1 (52.7–71.8) 70.9 (61.0 – 78.0) 0.001 Hb median (g/dl) (IR) 13.9 (12.5 – 14.7) 14.2 (13.0 – 15.2) 0.136 PLT median (x 109/l) (IR) 800 (669 – 1066) 778 (652 – 926) 0.453 WBC median (x 109/l) (IR) 9.2 (7.8 – 11.3) 8.6 (7.1 – 10.8) 0.121 Median interval diagnosis – CHT (mos) (IR) 0.9 (0 – 7.0) 1.7 (0.4 – 5.6) 0.194 *CV risk factors (n°/%): 0.454     0 20 (21.0) 17 (18.6)     1 42 (44.2) 44 (48.3)     ≥ 2 33 (34.8) 30 (33.1) Type of previous thrombosis (n°/%): 0.873     Arterial 78 (82.1) 67 (73.6)     Venous 17 (17.9) 24 (26.4) * Cardiovascular (CV) risk factors at diagnosis were considered the presence of arterial hypertension, diabetes, smoking attitude, and hypercholesterolemia. In the group A, 9 out 95 patients (9. 4%) reported thrombotic episodes (5 arterial and 4 venous) during follow-up compared to 23 out 91 patients (25. 2%) (13 arterial and 10 venous) in the group B (p=0. 004). Consequently, patients of group B had a significantly higher cumulative risk of thrombosis compared to patients of group A (p=0. 0029, CI95% 1. 5 – 6. 1, RR 3. 04). In addition, it is worth of note that there was no difference in the cumulative risk of thrombosis between the patients of group A and the 877 patients without previous thrombotic events (p=0. 303, CI95% 0. 64 – 3. 21, RR 1. 24) In conclusion, the prognostic role of a previous thrombotic event in ET patients seems to be related not to the occurrence per se of the event but mainly to the interval between the event and the diagnosis of ET. Disclosures: Tafuri: Sigma Tau Pharmaceuticals: Research Funding.

Description: Introduction . Elderly patients (pts) with Immune thrombocytopenia (ITP) may represent a clinical challenge since comorbidities and impaired functional capacity may reduce the therapeutic landscape and drug tolerability. Aims . To report ITP characteristics at diagnosis, and type/timing of treatment strategy, including response and toxicity rates in a cohort of elderly ITP pts. Methods. An electronic database was established to retrospectively collect clinical/laboratory data on elderly (age ≥60 yrs) pts that received at least one line of therapy for ITP in 11 Italian Hematology Centers. Data cut-off was July 2018. Treatment decisions were at the physician's discretion. Diagnosis and responses were assessed according to current guidelines and terminology. Infectious, thrombotic and hemorrhagic complications were graded according to the WHO scale. Comparisons of quantitative variables between groups were carried out by Wilcoxon-Mann-Whitney rank-sum test, and association between categorical variables (2-way tables) was tested by χ2 test. Cumulative incidences of infections, bleeding, and thrombosis were calculated considering death as competing risk (Fine and Gray model). Statistical significance was set at p

Description: Introduction. Availability of the 2 TPO-RAs Romiplostim (Rom) and Eltrombopag (El) offers an effective treatment option for primary ITP patients (pts). However, some pts are either not responsive or lose response - i.e. desired platelet (plt) count achieved but not sustained over time, or experience wide fluctuations in plt count with either TPO-RA. Adverse events may cause treatment discontinuation. Finally, ptÕs preference may be an important issue considering the different route and timing of administration of the two agents. Availability of two TPO-RAs for clinical use, with different molecular structure and site of binding within the TPO receptor, makes it appealing to try switching with the aim of overcoming treatment limitations of either agent. The present survey offers insight into outcome of TPO-RA switching in a group of ITP pts treated at 8 Centers representative of the Italian territory. Patients. Charts of ITP pts on treatment who underwent TPO-RA switch were retrospectively reviewed. Results. Between Jan 2009 and Feb 2015, 57 of 249 pts on TPO-RA (22,9%) underwent switch: El ˆ Rom 26/57 (45.6%), Rom ˆEl 31/57 (54.4%). Median age at 1st TPO-RA administration was 55 yrs (range 16-81); M/F = 23/34. Median disease duration prior to 1st TPO: 58 mos (range 2-648). Median lines of previous therapy 3 (range 1-6; splenectomy: 23/57, 40.4%). Overall 42/57 pts (73,7%) had received maximum product dose as per prescribing information prior to switch. Table 1 summarizes reasons for TPO-RA switch and outcome. Overall, 32/57 pts (56.1%) achieved, regained or maintained a response upon switching. The majority of pts (39/57, 68.5%) were switched for efficacy issues, i.e. failure to respond to 1st TPO (27 pts) or response loss (12 pts); among these 39 pts, 48.7% responded to the 2nd TPO-RA. One pt lost response to Rom because of development of neutralizing antibodies; response was regained upon switching to El. In this subgroup of pts, disease duration and lines of previous therapy (but not splenectomy status) seem to have an impact on response to switching. Each one month increase in disease duration determines a 0.7% decrease in the odds of achieving a response (WaldÕs test p=0.065). More than 2 lines of therapy determine a 72% decrease in the odds of achieving a response (WaldÕs test p=0.077). Either TPO-RA switch sequence was equally effective in yielding response (FisherÕs exact test p=0.752) and age at 1st TPO-RA had no impact on response. Of the 18 pts switched for reasons other than efficacy, 13 (72.2%) maintained a response on the 2nd TPO-RA: 5/6 switched for plt count instability (counts stabilized = 2/5 responding pts), 4/7 switched for ptÕs preference, 4/5 switched for side effects. Four pts (1 plt count instability, 3 ptÕs preference) underwent Òdouble switchÓ (i.e. Rom ˆ El ˆ Rom): re-exposure to Rom was not associated with response loss. Discussion. Switching enables approximately 56% of pts to achieve, regain or maintain a plt response; switching for inefficacy yields lower response rates (48.7%) compared to switching for reasons other than efficacy (72.2%) Plt counts fluctuation stabilized in 40% of pts. Re-exposure to R in the 4 pts who underwent Òdouble switchÓ was not associated with response loss, confirming absence of tachyphylaxis with this TPO-RA. Our results are in line with those reported by Khellaf (Haematologica 2013) and Gonzales-Porras (BJH 2014): TPO-RA switch can be a safe and appealing treatment option for ITP pts who experience suboptimal results with either agent. Table 1. REASON for SWITCHING n (%) NR (%) R (%) CR (%) All 57 (100) 25 (43.9) 14 (24.6) 18 (31.5) El-〉Rom 26 (45.6) 10 (38) 8 (31) 8 (31) Rom-〉El 31 (54.4) 10 (48.4) 6 (19.4) 10 (32.3) 1st TPO-RA failure 27 (47.4) 16 (59) 4 (15) 7 (26) El-〉Rom 15 7 (47) 3 (20) 5* (33) Rom-〉El 12 9 (75) 1 (8) 2 (17) Loss of response 12 (21.1) 4 (33) 2 (17) 6 (50) El-〉Rom 4 2 (50) 1 (25) 1 (25) Rom-〉El 8 2 (25) 1 (12.5) 5 (62.5) Plt count fluctuation 6 (10.5) 1 (17) 3 (50) 2 (33) El-〉Rom 2 0 1 1 Rom-〉El 4 1 2 1 PtÕs preference 7 (12.3) 3 (42.9) 2 (28.6) 2 (28.6) El-〉Rom 0 0 0 0 Rom-〉El 7 3 2 2 Adverse event¡¡ 5 (8.8) 1 (20.0) 3 (60.0) 1 (20.0) El-〉Rom 5 1 3 1 Rom-〉El 0 0 0 0 CR: complete response; R: response; NR: no response (Rodeghiero et al, Blood 2009) *1 NR secondary to neutralizing antibodies development ¡¡1 hepatic enzyme increase, 1 CPK increase; 2 skin rash; 1 retinal thrombosis. Disclosures De Stefano: Janssen Cilag: Research Funding; Shire: Speakers Bureau; Amgen: Speakers Bureau; Bruno Farmaceutici: Research Funding; Novartis: Research Funding, Speakers Bureau; Roche: Research Funding; Celgene: Speakers Bureau; GlaxoSmithKline: Speakers Bureau.

Description: Abstract 2056 Background: Recent international guidelines (Rodeghiero F, et al. Blood 113:2386–93, 2009) emphasize the importance of health-related quality of life (HRQOL) in patients with primary immune thrombocytopenia (pITP) and are advocating for more research in this area. However, very little research has been conducted on HRQOL of these patients. Aim: The main objective of this study was to identify specific limitations of HRQOL in pITP patients (ie, chronic, persistent and newly diagnosed patients) in comparison with their peers from the general population. Also, socio-demographic and clinical factors were considered to evaluate HRQOL impairment. Patients and Methods: Data were gathered through an ongoing multicenter observational study that recruits p-ITP patients. HRQOL was the primary endpoint of the study and was assessed with Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) that consists of 36 items covering eight generic health status/QoL domains: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). All scales ranging between 0 and 100 with higher scores representing better outcomes. Two summary scores, namely the physical component summary (PCS) and the mental component summary (MCS) are derived from a weighted combination of the eight scales. Mean SF-36 scores were compared to available national general population reference values and analyses were adjusted for age and gender. Based on previous research, eight points were considered to be a minimally important difference (MID) for the first eight SF-36 scales, while a difference of two points was judged as MID for the PCS and the MCS scores. A score difference at least equal to MID was considered as a clinically meaningful difference. Socio-demographic, clinical and laboratory data were also collected to investigate their association with HRQOL outcomes. Univariate and multivariate linear regression analyses were used. Results: To date of the 256 pITP patients included in this study, 69%, 16% and 15%, were diagnosed with chronic, persistent and newly diagnosed pITP respectively. Present analysis is based on 175 patients with HRQOL data currently available. At study participation, mean age of patients was 54 years (67% female and 33% male). At least one comorbidity was present in 53% of patients. The median time from initial diagnosis to study entry was 0.3, 8 and 77 months respectively for newly diagnosed, persistent and chronic patients. Age and gender adjusted comparisons with general population norms revealed worse outcomes for the following scales: RP (P65 years) suggested an almost uniform pattern in all scales with worse outcomes between pITP patients and population controls among the youngest groups. Statistically and clinically meaningful differences (ie, 〉8 points) were found in five out of the eight scales of the SF-36 in the youngest group of patients (18–54 years), when compared with their peers, while these differences were not present in the other age group categories. Comorbidity was the main factor influencing HRQOL by independently predicting worse HRQOL outcomes across all domains of the SF-36. SF-36 mean score differences in patients with or without comorbidity, were more than twice the magnitude of a clinically meaningful difference for PF and RP, being respectively: 69.7 vs. 87 and 51.3 vs. 68 points. Conclusions: This study suggests that HRQOL of p-ITP patients is far from optimal. In particular, role limitations (i.e., in work or other daily activities) due to physical health seems the major constraint faced by these patients when compared to their peers in the general population. Comorbidity seems the major factor associated with a poorer HRQOL profile. These findings need to be confirmed with a larger sample size and will eventually help guide the development of patient-centered supportive care programs. Disclosures: No relevant conflicts of interest to declare.