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Abstract: This retrospective study of the thrombocythemia Italian registry (RIT) documented that 71 (30.6%) out of 232 ET patients experienced 88 cardiovascular adverse events (CV-AEs) during anagrelide treatment (522 pt-y). The rate of CV-AEs was: 24.1% for palpitations, 4.3% for angina, 3.5% for arterial hypertension, 3.0% for congestive heart failure, 1.8% for arrhythmia, 0.9% for AMI, 0.4% for pericardial effusion. CV-AEs led to treatment discontinuation in nine (3.9%) patients, while in the remaining cases they were managed by pharmacological intervention and/or patient life style improvement. CV-AEs had no relationship with patient characteristics (including older age). A significant relationship was found only with a higher anagrelide induction dose. In the absence of any agreed protocol, a cardiovascular instrumental evaluation (CV-IE) was performed in 102 (44%) patients before commencement of anagrelide (with higher rate after the anagrelide/Xagrid EMA approval of 2004), and in 84 (36%) patients during treatment. Patients with and without CV-IEs, who resulted completely balanced for all their characteristics, did not significantly differ in the occurrence of CV-AEs. In conclusion, this study on ET patients treated with anagrelide shows that CV-AEs, equally distributed in younger and older subjects, were mostly mild and easily manageable, allowing safe treatment continuation in the majority of cases. Moreover, routinely performing a CV-IE did not appear to anticipate the occurrence of CV-AEs. [Copyright &y& Elsevier]

Highlights • Essential thrombocythemia (ET) has a risk of malignant transformation. • We determined transformation to acute myelogenous leukemia (AML). • Standardized incidence ratio of AML was high in ET patients on hydroxycarbamide. • No cases of AML occurred in ET patients treated with anagrelide. • Rates for non-AML cancers were similar in the two groups. Abstract EXELS, a post-marketing observational study, is the largest prospective study of high-risk essential thrombocythemia (ET) patients, with an observation time of 5 years. EXELS found higher event rates of acute leukemia transformation in patients treated with hydroxycarbamide (HC). In the current analysis, we report age-adjusted rates of malignant transformation from 3460 EXELS patients exposed to HC, anagrelide (ANA), or both. At registration, 481 patients had ANA treatment without HC exposure, 2305 had HC without ANA exposure, and 674 had been exposed to both. Standard incidence ratios (SIRs) were calculated using data from the Cancer Incidence in Five Continents database to account for differences in age-, gender-, and country-specific background rates. SIRs for acute myelogenous leukemia (AML) were high in ET patients. SIRs for AML were high in HC-treated patients, but AML was rare in ANA-treated patients; no cases of AML were found in patients only treated with ANA. No statistically significant difference was seen between SIRs for ANA and HC treatment for AML or skin cancer. SIRs for other cancers were similar in the HC and ANA groups and close to 1, indicating little difference in risk. Although statistically inconclusive, this study strengthens concerns regarding possible leukemogenic risk with HC treatment. (NCT00202644) [ABSTRACT FROM AUTHOR]

In this prospective observational single-center study, 55 patients with essential thrombocythemia who were candidates for second line treatment with anagrelide (ANA) received a preliminary cardiovascular (CV) clinical, instrumental and biochemical evaluation (CV history and symptoms, CV risk factors, blood pressure, heart rate, ECG and ECHO-cardio parameters, Troponin I, NT-proBNP). After this in-depth CV screening, 54 out of 55 patients were deemed to be fit for ANA treatment. Thirty-eight of the 55 patients received ANA treatment for a median of 36 months (range 3–48), and were monitored using the same CV evaluation. Fourteen of these 38 patients manifested CV adverse events (10 palpitation, 4 edema, 2 arterial hypertension, 2 acute myocardial infarction) that were not predicted by the in-depth CV evaluation, and that led to ANA withdrawal in only one case (non-cardiac refractory edema). In conclusion, the planned in-depth CV evaluation did not appear to be necessary in ET patients to evaluate their suitability for ANA treatment, and, moreover, was not able to predict the occurrence of CV adverse events during ANA treatment. Nevertheless, the CV adverse events (mostly palpitations and edema) were easily managed by the hematologists, and required the cardiologist involvement in very few selected cases. [ABSTRACT FROM AUTHOR]

Abstract: EXELS is an ongoing phase IV non-interventional study; 3643 high-risk patients with essential thrombocythemia (ET) were recruited across 13 European countries. We report patient characteristics and cytoreductive treatment patterns of ET across Europe. Hydroxycarbamide (HC; 64.3%) and anagrelide (22.0%) were the two main cytoreductive treatments prescribed. The proportions of patients taking either HC or anagrelide varied across countries, as did the number of patients receiving anti-aggregatory therapy in addition to cytoreductive treatment. This real-world evidence demonstrates that, generally, treatment patterns of ET across Europe adhere to expert recommendations, with some notable variations between countries. [Copyright &y& Elsevier]