TARGET: a survey of real-world management of chronic myeloid leukaemia across 33 countries.

Despite the availability of guidelines for the management of chronic myeloid leukaemia (CML), various issues may prevent their successful implementation. The TARGET survey examined real-world management of CML patients compared with international recommendations. This online survey was completed in 2017. Results were discussed by a Steering Committee (SC) of eight international haematologists, challenges were identified and practical solutions developed. Of the 1008 haematologists invited (33 countries), 614 completed the survey. Gaps regarding treatment efficacy and molecular monitoring were identified. Half of the physicians did not perform three-monthly testing of during the initial 12 months of treatment, citing cost as the major barrier, although they know it should be done. Treatment-free remission was not considered a primary treatment goal or as a priority factor influencing treatment decisions. European Leukemia Net guidelines interpretation was generally acceptable, but awareness regarding management of persistent adverse events was poor. Practical solutions proposed by the SC were mostly focused on enhancing physician education and awareness, or encouraging hospitals to work with the government, in order to improve the quality of BCR-ABL testing. Gaps in current CML management were identified compared with international recommendations, which the proposed practical solutions would help to address.

Efficacy and safety profile of long-term exposure to lenalidomide in patients with recurrent multiple myeloma.

BACKGROUND: Lenalidomide in combination with dexamethasone (Len/Dex) is indicated for patients with recurrent/refractory multiple myeloma (RRMM) who were treated with 1 prior therapy until evidence of disease progression. The objective of the current study was to determine the efficacy and safety profile of long-term exposure to Len/Dex. METHODS: A total of 50 patients with RRMM who were treated with long-term Len for ≥ 2 years from 2 Intergroupe Francophone du Myélome (IFM) centers (Lille and Nancy) were included in the current study. RESULTS: The median age of the patients was 58 years, with 30% of the patients aged >65 years, 49% having an International Staging System stage of 2 and 3, 12% having severe renal insufficiency, and 8% demonstrating an adverse result on fluorescence in situ hybridization. Approximately 56% of the patients received treatment with Len/Dex for ≥ 3 years. The median duration of treatment with Len/Dex was 3 years (range, 2 years-7 years). The response rates for partial response or better and very good partial response or better for the overall cohort were 96% and 74%, respectively, which is similar to patients exposed to Len for ≥ 3 years. With a median follow-up of 4 years, 19 (38%) patients had stopped treatment with Len/Dex. The time to disease progression rate at 37 months was 78% and 91%, respectively, in patients exposed to Len for 2 years to <3 years and for ≥ 3 years (P=025). The safety profile was manageable, similar to that of Len when administered for a shorter period of time; 16% of patients had grade 3 to 4 neutropenia, 6% had thrombopenia, 6% had anemia, and 20% experienced thromboembolic events, all of venous type. The annual incidence rate of second primary malignancy was 1.96% in the current series. CONCLUSIONS: The results of the current study confirmed that the Len/Dex combination is feasible for long-term use in patients with RRMM, with a significant benefit noted in terms of time to disease progression for prolonged treatment with Len/Dex.

International real-world study of DLL3 expression in patients with small cell lung cancer.

OBJECTIVES: Expression of the Notch-family ligand delta-like protein 3 (DLL3), a potential therapeutic target in small cell lung cancer (SCLC), has not been assessed in the real-world setting. To identify the real-world utility of DLL3 as an SCLC therapeutic target, we performed the largest retrospective international noninterventional study to date to evaluate DLL3 prevalence in SCLC patients. MATERIALS AND METHODS: DLL3 expression was assessed using immunohistochemistry in archived histological and cytological specimens (independent and paired) and correlated to patient demographics, clinical disease characteristics, and survival. The primary endpoint was the proportion of patients with DLL3 expression in ≥25 % of tumor cells. DLL3 expression concordance was assessed in paired specimens. RESULTS: Independent tumor specimens were collected from 1073 patients. The mean age at biopsy was 66 years (SD, 10); 682 (64 %) patients were male. Paired specimens were collected from 36 patients. The mean age at biopsy was 62 years (SD, 11); 16 (44 %) patients were male. Most patients had ECOG performance status of 0-1, were smokers/ex-smokers, and received ≥1 prior therapy. Positive DLL3 expression (defined as ≥25 % of tumor cells) was identified in 895/1050 (85 %) patients with 1 specimen and evaluable DLL3 expression; 719/1050 (68 %) patients had high DLL3 expression (defined as ≥75 % of tumor cells). DLL3 expression concordance was 88 % between paired specimens (n = 17; Cohen's kappa P value, .9412). There was no significant difference in median overall survival from SCLC diagnosis for evaluable patients with nonmissing data based on DLL3 expression (negative DLL3 expression [n = 139], 9.5 months; positive DLL3 expression [n = 747], 9.5 months; all evaluable patients [n = 893, 9.5 months). CONCLUSION: These real-world epidemiologic findings indicate that DLL3 is robustly expressed across SCLC disease stages and remains stable despite treatment, consistent with available clinical trial data. There was no prognostic role for DLL3 observed in this study for overall survival.

Safety and efficacy of nilotinib in routine clinical practice in patients with chronic myeloid leukemia in chronic or accelerated phase with resistance or intolerance to imatinib: results from the NOVEL study.

BACKGROUND: Nilotinib, a second-generation tyrosine kinase inhibitor (TKI), is approved for the treatment of patients with chronic myeloid leukemia (CML) in many countries, including Taiwan. Though a number of controlled clinical trials have demonstrated the safety and efficacy of nilotinib, studies assessing the safety and efficacy of nilotinib in routine clinical practice are limited. METHODS: The current study was an open-label, single-arm study conducted across 12 centers in Taiwan in adult patients with CML in chronic or accelerated phase with confirmed Ph+ chromosome (or BCR-ABL) and resistant or intolerant to one or more previous TKIs. The primary objective was to collect the long-term safety data in patients treated with nilotinib 400 mg, twice daily for up to 2 years. RESULTS: The study enrolled 85 patients with CML, including 76 in the chronic phase (CML-CP) and 9 in the accelerated phase (CML-AP). Overall, 1166 adverse events (AEs) were reported in 80 patients (94.1%), of which 70 AEs (6%) in 28 patients (32.9%) were serious and 336 AEs (28.8%) reported in 60 patients (70.6%) were drug-related. Common drug-related AEs were thrombocytopenia (21.2%), increased alanine aminotransferase (21.2%) and pruritus (17.7%). Of the 85 patients, 19 switched from imatinib due to intolerance - AEs were resolved in 16 of these 19 patients (84.2%). By 24 months, the cumulative rates of complete cytogenetic response (CCyR), major molecular response (MMR), MR4.0 (BCR-ABL1IS ⩽0.01%) and MR4.5 (BCR-ABL1IS ⩽0.0032%) were 75.3, 56.8, 16.2 and 7.4%, respectively. Patients with CML-CP at baseline had higher overall survival (OS) and progression-free survival (PFS) than those with CML-AP. CONCLUSION: This is the first study that demonstrated that nilotinib is effective and well-tolerated in patients resistant or intolerant to imatinib in the real-world setting in Taiwan, reflecting effective management of CML by physicians under routine clinical practice in Taiwan.

Correlation between peripheral blood pressure and pulse-wave velocity values in the institutionalized elderly persons 80 years of age and older: the PARTAGE study.

BACKGROUND: Carotid-femoral pulse-wave velocity (PWV) provides a comprehensive noninvasive indication of arterial stiffness, and is now established as a strong marker of cardiovascular disease (CVD). The correlation between peripheral blood pressure (BP) and PWV and their respective influences on mortality have been poorly studied in the elderly. Our objective was to analyze this correlation in nursing-home residents over 80 years of age, with the view that the results of this could ultimately be helpful in implementing strategies for the diagnosis and long-term follow-up of CVD and mortality in the very elderly population. METHODS: The Predictive Value of Blood Pressure and Arterial Stiffness in Institutionalized Very Aged Population (PARTAGE) study is a 2-year cohort study of 1,130 subjects living in 72 nursing homes in France and Italy. The correlation between baseline systolic and diastolic blood pressure (SBP and DBP, respectively) and baseline PWV (measured with a PulsePen® tonometer) was studied in 1,071 subjects for whom PWV measurements were available. RESULTS: Correlations between peripheral BP and PWV were significant but weak, with r = 0.24 for self-measured SBP, r = 0.30 for casual SBP, r = 0.11 for self-measured DBP, r = 0.14 for casual DBP, and r = 0.26 for casual pulse pressure (PP). A trend toward a weaker correlation was observed in the older age group for self-measured SBP and in the group with a lower level of activities of daily living (ADL) for self-measured SBP and DBP. CONCLUSIONS: These findings suggest that SBP, DBP, and PWV provide different information in the very elderly. The results of the prospective, longitudinal, long-term PARTAGE study will allow further insight into this and provide additional in-depth information about the respective prognostic value of the measurement of peripheral BP and PWV.

A simple nomogram for early prediction of myocardial reperfusion after pre-hospital thrombolysis.

AIMS: To discriminate early ST-segment elevation myocardial infarction (STEMI) presenters at a high probability of successful pre-hospital thrombolysis (PHT) using a simple nomogram based on independent predictors of complete ST resolution. METHODS AND RESULTS: OPTIMAL was an observational, prospective study undertaken at 79 medical centres in France in patients with STEMI undergoing pre-hospital thrombolysis (PHT) within six hours of symptom onset and coronary angiography within six hours of thrombolysis. The baseline and pre-coronary angiography ECGs of 800 patients were analysed. The main outcome measure was ST segment resolution ≥ 70%. ST resolution was associated with a significant reduction in mortality (1.8% vs. 4.3%; p=0.05). After multivariable logistic regression analysis, five independent predictors of successful myocardial reperfusion were identified: ≤ 1 h between pain onset and thrombolysis (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.18-2.62); body mass index (BMI) <30 kg/m2 (OR 1.74, CI 1.12-2.72); current/previous smoking (OR 1.71, CI 1.21-2.43); non-anterior infarct territory (OR 1.75, CI 1.27-2.41); and maximum amplitude of ST elevation <3 mm (OR 1.83, CI 1.32-2.54). The C-statistic of the model was 0.71 (95% CI 0.67-0.74). Using these five independent factors, a simple nomogram was developed to assess the probability of ST resolution after PHT. This nomogram allows discrimination of probabilities ranging from 13 to 72%. CONCLUSIONS: This simple nomogram can predict the probability of successful myocardial reperfusion after thrombolysis. This may be useful in the triage of STEMI presenters.

Blood pressure and pulse wave velocity values in the institutionalized elderly aged 80 and over: baseline of the PARTAGE study.

OBJECTIVE: The aim of the longitudinal study PARTAGE (predictive values of blood pressure and arterial stiffness in institutionalized very aged population) was to determine the predictive value of blood pressure (BP) and arterial stiffness for overall mortality, major cardiovascular events and cognitive decline in a large population of institutionalized patients aged 80 and over. In the study herein, we present the baseline data values of this study. METHODS: A total of 1130 patients were recruited (878 women), living in French and Italian nursing homes. Clinical and 3-day self-measurements of BP were conducted. Aortic and upper limb pulse wave velocity were obtained using a PulsePen tonometer. RESULTS: Of this population, 76% of women and 60% of men had a known hypertension and over 91% of the patients were under antihypertensive treatment; 51% of the treated hypertensive patients were well controlled (systolic BP <140 mmHg). No significant differences were found between clinical and self-measured BP. With age, there was an increase in pulse pressure (P < 0.001) due to a decrease in diastolic BP (P < 0.001), without any increase in systolic BP. Aortic but not peripheral pulse wave velocity significantly increased with age (P < 0.005). CONCLUSION: Baseline values obtained herein demonstrate that elderly patients living in nursing homes present hemodynamic characteristics which are different to those described in community-living elderly populations, and indicate the interest of assessing, in longitudinal studies, the role of BP and arterial stiffness in morbidity and mortality in this population.