Prospective Non-interventional Study Research Articles

Влияние самоконтроля на течение и исходы гестационного сахарного диабета

Gestational diabetes mellitus is characterized by an increased risk of fetal macrosomia and obstetric complications during childbirth, as well as the development of type 2 diabetes in the mother after pregnancy. Timely diagnosis and treatment of hyperglycemia during pregnancy reduces adverse pregnancy outcomes. The first step towards tight glucose control during pregnancy is self-monitoring of glycemia. Aim: to evaluate the effectiveness of regular glycemic control using a Satellite express glucometer calibrated on capillary whole blood in patients with gestational diabetes mellitus (GDM) in outpatient practice. Material and methods. The 96-week prospective observational non-interventional study included 150 patients with GDM. In women with confirmed GDM, blood glucose was measured using a satellite express glucometer. At each visit, further tactics for the treatment of GDM were determined based on the results of glycemia (data from the self-monitoring diary). Until the 34th week of pregnancy, an endocrinologist was consulted with a frequency of 1 time in 2 weeks in the form of a medical appointment and telephone contact. After 34 weeks of pregnancy, consultation of an endocrinologist with a frequency of 1 time per week. 6–12 weeks after delivery, an oral glucose tolerance test and consultation with an endocrinologist were performed to assess the degree of carbohydrate metabolism disorder. Results. The participation of 138 (92%) patients in the study ended in childbirth, 12 (8%) patients dropped out of the study ahead of schedule. Spontaneous abortions were noted in patients who performed self-monitoring of glycemia 0–1 times a day, independent births were more often observed in patients who performed self-monitoring 3–4 times a day, and these patients also had more stable glycemic indices. 9 patients out of 138 gave birth to children weighing 4000 g or more. The weight of the rest of the children at birth did not exceed 3500 g. Conclusion. A well-controlled course of GDM, adequate self-monitoring and dynamic observation of women allows delivery to be carried out within the generally accepted terms without worsening its outcomes.

“Extrafine single inhaler triple therapy effect on health status, lung function and adherence in COPD patients: A Panhellenic prospective non-interventional study – The TRIBUNE study”

The extrafine single inhaler triple therapy (efSITT) containing beclometasone dipropionate/formoterol fumarate/glycopyrronium 87/5/9 μg has proved to be efficacious in patients with Chronic Obstructive Pulmonary Disease (COPD) in randomized control trials. TRIBUNE study aimed to assess the efSITT effectiveness on health status, lung function, adherence and rescue medication use in COPD patients in Greece in a real-world setting.This was a 24-week prospective, multicenter, observational study in 1,195 patients with moderate/severe COPD and history of at least one exacerbation during the previous year despite dual therapy. Health status (COPD Assessment Test/CAT), lung function parameters and rescue medication use were recorded at baseline, 3 (Visit 2/V2) and 6 months (Visit 3/V3) after treatment. Adherence (Test of Adherence to Inhalers/TAI) and self-reported overall impression of health condition change (Visual Analogue Scale/VAS) were recorded at V2 and V3.Mean CAT score decreased from 20.9 points at V1, to 15.1 at V2 and 13 at V3 (p < 0.001, all pair comparisons). 85.9% of patients achieved a CAT decrease of minimal clinically important difference (MCID) or more (≥2) at V3, compared to V1. Mean FEV1 increased from 1.4 ± 0.5 L on V1, to 1.6 ± 0.5 L on V3 (p < 0.001, N = 275). The percentage of patients with “good adherence” increased from 58.4% (V2) to 64.0% (V3). Rescue medication use and VAS also significantly improved.The efSITT achieves improved outcomes on health status, lung function and rescue medication use as well as satisfactory adherence and patient-reported improvement of health condition, in moderate/severe COPD patients previously treated with a dual combination in a Greek real-world setting.

P003 ROSE trial: A prospective non-interventional study to assess the quality of life (QoL) of premenopausal patients with early breast cancer receiving triptorelin as ovarian function suppression

P003 ROSE trial: A prospective non-interventional study to assess the quality of life (QoL) of premenopausal patients with early breast cancer receiving triptorelin as ovarian function suppression

Genomic characteristics and clinical significance of CD56+ circulating tumor cells in small cell lung cancer

Circulating tumor cells (CTC) have been studied in various solid tumors but clinical utility of CTC in small cell lung cancer (SCLC) remains unclear. The aim of the CTC-CPC study was to develop an EpCAM-independent CTC isolation method allowing isolation of a broader range of living CTC from SCLC and decipher their genomic and biological characteristics. CTC-CPC is a monocentric prospective non-interventional study including treatment-naïve newly diagnosed SCLC. CD56+ CTC were isolated from whole blood samples, at diagnosis and relapse after first-line treatment and submitted to whole-exome-sequencing (WES). Phenotypic study confirms tumor lineage and tumorigenic properties of isolated cells for the 4 patients analyzed with WES. WES of CD56+ CTC and matched tumor biopsy reveal genomic alteration frequently impaired in SCLC. At diagnosis CD56+ CTC were characterized by a high mutation load, a distinct mutational profile and a unique genomic signature, compared to match tumors biopsies. In addition to classical pathways altered in SCLC, we found new biological processes specifically affected in CD56+ CTC at diagnosis. High numeration of CD56+ CTC (> 7/ml) at diagnosis was associated with ES-SCLC. Comparing CD56+ CTC isolated at diagnosis and relapse, we identify differentially altered oncogenic pathways (e.g. DLL3 or MAPK pathway). We report a versatile method of CD56+ CTC detection in SCLC. Numeration of CD56+ CTC at diagnosis is correlated with disease extension. Isolated CD56+ CTC are tumorigenic and show a distinct mutational profile. We report a minimal gene set as a unique signature of CD56+ CTC and identify new affected biological pathways enriched in EpCAM-independent isolated CTC in SCLC.

Impact of access to treatment on patient-reported outcomes among rheumatoid arthritis patients with tDMARDs and bDMARDS in two Latin-American countries: A prospective observational study.

A noninterventional prospective study was performed in Colombia and Peru. The aim was to describe the impact of access to treatment on Patient-reported outcomes (PRO) in patients with Rheumatoid arthritis (RA) after failure to conventional disease-modifying antirheumatic drugs (DMARDs) in real-life conditions. The impact of access to treatment was measured by access barriers, time to supply (TtS) and interruption evaluating their effect in changes of PROs between baseline and 6-month follow-up between February 2017 and November 2019. The association of access to care with disease activity, functional status, health-related quality of life was assessed using bivariate and multivariable analysis. Results are expressed in least mean difference; TtS in mean number of days for delivery of treatment at baseline. Variability measures were standard deviationand standard error. One hundred seventy patients were recruited, 70 treated with tofacitinib and 100 with biological DMARDs. Thirty-nine patients reported access barriers. The mean of TtS was 23 ± 38.83 days. The difference from baseline to 6-month visit in PROs were affected by access barriers and interruptions. There was not statistically significant difference in the of PRO's score among visits in patients that reported delay of supply of more than 23 days compared to patients with less days of delay. This study suggested the access to treatment can affect the response to the treatment at 6 months of follow-up. There seems to be no effect in the PROs for delay of TtS during the studied period.

The Acute Optic Neuritis Network (ACON): Study protocol of a non-interventional prospective multicenter study on diagnosis and treatment of acute optic neuritis.

ClinicalTrials.gov, identifier: NCT05605951.

CaboCombo: A prospective international non-interventional study of first-line cabozantinib plus nivolumab for the treatment of patients with advanced renal cell carcinoma.

TPS740 Background: The combination of cabozantinib plus nivolumab (Cabo + Nivo) was approved in Europe in 2021 for the first-line (1L) treatment of patients with advanced renal cell carcinoma (aRCC) based on evidence from the phase 3 CheckMate 9ER trial. In the CheckMate 9ER trial (N = 651), Cabo + Nivo improved overall survival (hazard ratio [HR] 0.70 [95% confidence interval: 0.55–0.90]; p = 0.0043) and progression-free survival (HR 0.56 [95% CI: 0.46–0.68]; p ≤ 0.0001) versus sunitinib. There is clinical interest in the effectiveness and tolerability of Cabo + Nivo as used in routine cancer care. Methods: CaboCombo is a prospective, international, real-world non-interventional study to evaluate the effectiveness and tolerability of 1L Cabo + Nivo in adults (aged ≥ 18 years) with aRCC with a clear-cell component. In total 311 patients will be enrolled across 70 centers in countries where 1L Cabo + Nivo has marketing authorization and reimbursement. The decision to prescribe Cabo + Nivo will be made prior to, and independently from, the decision to enroll patients. The primary endpoint is real-world landmark overall survival assessed 18 months after Cabo + Nivo initiation. Secondary endpoints include: real-world treatment patterns; median progression-free survival; objective response rate; duration of response; disease control rate; time to response; treatment-emergent adverse events, and changes in disease-related symptoms and pain during the treatment period (assessed by the Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index – Disease Related Symptoms questionnaire, and the Numerical Pain Rating Scale). Patients will be enrolled over 24 months and followed for up to 42 months. The nature and timing of study visits and assessments will be as per usual care at each participating center; no additional diagnostic or monitoring procedures will be conducted. Treatment will continue until disease progression, unacceptable toxicity or withdrawal of participant consent. Two interim analyses will be conducted, the first a description of baseline characteristics when at least 50% of participants have been recruited. No changes in study design or conduct will be made based on the results of these analyses. Clinical trial information: NCT05361434 .

The results of systemic thrombolytic therapy for acute ischemic stroke in women and men depending on the stroke risk factors

Background: Systemic thrombolytic therapy (STLT) with alteplase is the method of choice in all patients with acute ischemic stroke (IS) within the first 4.5 hours after the symptom onset. There is a noticeable difference between men and women in the clinical characteristics and results of stroke treatment; however, results of studies have been contradictory.&#x0D; Aim: To evaluate the efficacy of STLT with alteplase in women compared to men, depending on the presence of some risk factors for stroke.&#x0D; Materials and methods: This open-label prospective observational non-interventional cohort study of STLT in IS included 209 patients (102 women, the main group, and 107 men, or the comparison group) aged 32 to 86 years. All patients received STLT with alteplase within 4.5 hours from the onset of IS symptoms. The primary endpoint of the study was 28-day survival, and the secondary endpoint was the achievement of mobility independence (0 to 2 points by the modified Rankin Scale (mRS)).&#x0D; Results: The demographic and clinical patient characteristics of both groups were comparable, but women were on average 5 years older than men (p = 0.003). The index IS was not the first one in 31.4% of women and 23.4% of men (p 0.05). There were no significant differences in the severity of stroke and the timing of STLT. Men had a high mortality rate in the acute period of IS, but the difference was non-significant. PST-STLT hemorrhagic transformation was more common in men, with the difference being non-significant (2 0.743, p = 0.389). Women were more likely to have type 2 diabetes mellitus (DM2) (37.3% and 20.6%, respectively, 2 7.111, p = 0.008). In women, there was a trend towards better symptom regression by about 1 point (p = 0.129). The women with DM2 had a 13% higher survival than men (p = 0.038). The numbers of patients achieving independence (02 points on the mRS scale) by Day 28 was not different (56 women and 52 men). No between-groups differences were found in the numbers of patients with arterial hypertension and atrial fibrillation. Only 13 women (12.75%) and 21 men (20%) had a normal body mass index, while 56.3% of women and 46.7% of men had obesity 2 or 3 grades, with the gender differences being non-significant.&#x0D; Conclusion: In women, who have received STLT in the acute period of IS, the death rates and the functional outcomes were non-inferior to those in men, despite their older age, hyperglycemia in the acute period and past history of DM2. The risk factors for stroke in women, compared to men, could be the potential cause of more frequent IS recurrence (every third case in women and every fourth in men was recurrent). Despite a number of negative factors (age, obesity, metabolic syndrome, hyperglycemia, DM2, atrial fibrillation), there was a trend towards better outcomes of STLT in women.

P415 Real-world data in Inflammatory Bowel Diseases on vedolizumab therapy: Interim analysis of the non-interventional LISTEN II study

Abstract Background Vedolizumab (VDZ) is a gut-selective anti-lymphocyte trafficking integrin antibody and is approved for treating patients with moderately to severely active UC (ulcerative colitis) and CD (Crohn’s disease) intravenously (IV) or subcutaneously (SC). The LISTEN II study aims to determine patient characteristics and effectiveness in patients treated with VDZ in a real-world setting. Methods LISTEN II is a multicentre, prospective non-interventional study in Germany. Adult patients with UC or CD, for whom the physician has decided to either initiate VDZ IV or switch from IV to SC, are included. Data on patient characteristics, modalities of VDZ use and disease activity (pMayo, HBI) are followed up quarterly for up to one year per routine practice. In addition, patient reported outcomes (PROs) confirmed as relevant in the previous LISTEN I study (e.g. rectal bleeding and general wellbeing) are recorded via an app (ePRO). Results Data of 198 UC patients (50% female, 6.0 years median disease duration) and 116 CD patients (56% female, 10.9 years median disease duration) with a mean age of 40 years were included in this interim analysis. VDZ treatment was newly initiated IV in 164 UC patients and 98 CD patients (start) and switched from IV to SC by 34 UC and 18 CD patients (switch) at study inclusion. At baseline corticosteroids were documented as used in 70% and 56% of UC and CD start-patients in the year prior to enrollment. Burden of disease was classified as high (pMayo&amp;gt;4) in 51% of UC patients at baseline and decreased to 15% at 3 months. For CD patients, proportion of high burdened patients (HBI&amp;gt;7) was 27% at baseline and 12% at month 3 (Figure 1). In this period, total mean pMayo score decreased in UC patients from 4.3±2.5 (start: 4.9±2.1; switch: 1.0±1.3) to 2.2±2.2 (start: 2.5±2.2; switch:1.0±1.6) and total mean HBI score from 5.4±4.4 (start: 5.8±4.5; switch: 3.5±3.7) to 3.3±3.4 (start: 3.4±3.4, switch: 2.8±3.3) in CD patients (Figure 2). UC patients using the ePRO (N=152, mean age: 39 years, 49% female) reported from ePRO initiation up to month 3 a mean score decrease for rectal bleeding (range 0-3) from 1.3 to 0.6, for general well-being (range 0-4) from 1.7 to 1.3 and for impact on work productivity (range 0-10) from 3.7 to 2.3 points. Conclusion LISTEN II real-world data support the effectiveness of VDZ treatment in UC and CD patients. Patients starting VDZ IV showed a higher disease activity at baseline which decreased under VDZ treatment. Switching of VDZ IV to SC was mainly performed in patients with low disease burden under VDZ treatment, resulting in maintained therapeutic effectiveness. Also PROs of UC patients show an improvement supporting benefit with VDZ treatment.

Latent iron deficiency therapy in pregnant women

According to various studies, the overall population incidence of latent iron deficiency (LID) ranges from 70% and more. However, routine tests cannot detect LID during preconception examination and in the first trimester of pregnancy; therefore, women receive no proper treatment, and iron deficiency manifest in the second and third trimesters of pregnancy. LID causes hypoxia, leading to pregnancy, labor, and postpartum complications.&#x0D; Aim. To evaluate the effectiveness of iron with folic acid supplements compared to vitamin-mineral complexes in pregnant women with LID to improve maternal and perinatal outcomes.&#x0D; Materials and methods. A prospective cohort non-interventional study (observational program) in real clinical practice was conducted. In total 461 pregnant women aged 19 to 35 with LID were included in the study. During the study, women were divided into two groups according to the method of LID correction: administration of iron sulfate 247.25 mg, which corresponds to an iron content of 80 mg + folic acid 350 g (Gyno-Tardyferon), or vitamin-mineral complexes with an iron content of 1418 mg. Routine complete blood count, serum iron, serum ferritin, and transferrin were monitored over time.&#x0D; Results. Gyno-Tardyferon showed high therapeutic and prophylactic efficacy; the rate of favorable outcomes was 100% and 35% for multivitamin iron-containing complexes. No LID progression to manifest iron deficiency during pregnancy can also be considered a favorable outcome.&#x0D; Conclusion. The results showed that timely treatment of LID with an iron-containing medication (Gyno-Tardyferon) prevents manifested iron deficiency and hemic and circulatory hypoxia, which ultimately reduces the rate of pregnancy, labor, and postpartum complications.

Approaches to the diagnosis and treatment of patients with stage III—IV non-small cell lung cancer in Russia. Preliminary results of a prospective multicenter non-interventional observational study KARL

Approaches to the diagnosis and treatment of patients with stage III—IV non-small cell lung cancer in Russia. Preliminary results of a prospective multicenter non-interventional observational study KARL

REFLECT: prospective multicenter non-interventional study evaluating the effectiveness and safety of Sandoz rituximab (SDZ-RTX; Rixathon®) in combination with CHOP for the treatment of patients with previously untreated CD20-positive diffuse large B-cell lymphoma.

REFLECT is the first prospective study of Sandoz biosimilar rituximab (SDZ-RTX) in patients with diffuse large B-cell lymphoma (DLBCL). To evaluate the 2-year effectiveness and safety of SDZ-RTX as first-line treatment for DLBCL. Real-world, multicenter, open-label, single-arm, non-interventional, post-approval study of SDZ-RTX in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with treatment-naïve CD20‑positive DLBCL. Treatment-naïve, CD20-positive adult patients (⩾18 years) with DLBCL eligible for therapy with R-CHOP were treated with SDZ-RTX-CHOP every 2 or 3 weeks for 6-8 cycles. The effectiveness of SDZ-RTX was measured by the complete response (CR) rate at the end of R-CHOP treatment, as assessed by the treating physician. Progression-free survival (PFS) was assessed at 24 months. A total of 169 patients [52.1% female, median (range) age 70 (24-94) years] with DLBCL were included in the full analysis set. At baseline, 19.5% and 24.3% of patients had Ann Arbor disease stage III or IV, respectively, and most patients (80.5%) had Eastern Cooperative Oncology Group Performance Status of 0 or 1. A total of 100 (59.2%) patients completed the 24-month observation period. In total, 110 [65.1%; 95% confidence interval (CI): 57.4-72.3] patients achieved CR as best response and 50 (29.6%; 95% CI: 22.8-37.1) patients achieved partial response. Overall best response rate was 94.7% (95% CI: 90.1-97.5). One-year PFS was 84.9% (95% CI: 78.2-89.6), while 2-year PFS was 78.5% (95% CI: 70.9-84.4); median PFS was not reached within the observational period. A total of 143 (84.6%) patients experienced ⩾1 adverse event, 53 (31.4%) of which were suspected to be related to study drug. This real-world, 2-year study reconfirms that first-line treatment of CD20-positive DLBCL with R-CHOP using SDZ-RTX is effective and well tolerated. N/A.

Fatigue visual analogue scale score correlates with quality of life in cancer patients receiving epoetin alfa (Sandoz) for chemotherapy-induced anaemia: The CIROCO study

PurposeAvailable tools to measure fatigue and health-related quality of life (HRQoL) in cancer patients are often difficult to use in clinical practice. The fatigue visual analogue scale (VAS) provides a simple method to assess fatigue. This study evaluated the correlation between HRQoL and fatigue perceived by cancer patients undergoing chemotherapy. MethodsThis was a non-interventional prospective study of adult cancer patients in France presenting with chemotherapy-induced anaemia (CIA) treated with epoetin alfa (Sandoz). Data were collected using an electronic case report form at study inclusion (T0), after 2-3 chemotherapy cycles (T1) and after 4-6 cycles (T2). ResultsThe study included 982 patients from September 2015 to October 2017. Overall, there was a negative correlation between fatigue VAS and HRQoL. The overall haemoglobin (Hb) change between T0 and T2 was +17.8 % (± 18.1 %). Fatigue assessed by both patients and physicians showed a clinically significant improvement during the study. Global HRQoL also increased. ConclusionTreatment of CIA with epoetin alfa (Sandoz) improved Hb levels, fatigue, and HRQoL, with a correlation observed between fatigue VAS score and HRQoL. Fatigue VAS could act as a simple alternative to more complex methods to measure HRQoL; however, further analyses are required to confirm this association.

Treatment with aripiprazole once-monthly injectable formulation is effective in improving symptoms and global functioning in schizophrenia with and without comorbid substance use - a post hoc analysis of the ReLiAM study.

ReLiAM, Real-Life Assessment of Abilify Maintena, was the first reported long-term prospective non-interventional study for patients with schizophrenia treated with aripiprazole once-monthly injectable formulation (AOM) under real-life conditions. ReLiAM's primary aim was to evaluate the evolution of global functional status in patients treated with AOM for 12months in Canada. The objective of this post hoc analysis of the ReLiAM study is to investigate the treatment effects of real-life use of AOM over a 1-year period in the subgroup of patients with reported substance use compared with patients without substance use. The results of this post hoc analysis demonstrate that treatment with AOM for 12months in patients with schizophrenia was comparably effective in improving global functioning in subgroups of patients with and without concomitant substance use. These results support the use of AOM for the treatment of schizophrenia in patients with or without concomitant substance use. ClinicalTrials.gov NCT02131415, first posted on May 6, 2014. Overall trial status: Terminated.

Predictors of participants’ retention—socioeconomic factors or nonadherence: insights from a urological clinical prospective study

BackgroundTo investigate various patient-level variables, specifically socioeconomic status, as risk factors for withdrawal in a recently completed clinical study. We specifically investigated a non-interventional prospective study assessing the role of novel imaging as a biomarker for cancer upgradation in prostate cancer for this objective.MethodsIn this retrospective analysis, we assessed the association between various patient-level factors including clinic-demographic factors, socioeconomic status, and the number of non-adherences with the participants’ retention or withdrawal from the study. For socioeconomic status (SES), we used the zip code–based Economic Innovation Group Distressed Community Index (DCI) which classifies into five even distress tiers: prosperous, comfortable, mid-tier, at-risk, or distressed. Low SES was defined as those with a DCI Distress tier of at-risk or distressed. We compared values between the two retention and withdrawal groups using t-test, chi-square test, and logistic regression analysis.ResultsOf 273 men screened, 123 men were enrolled. Among them, 86.2% (106/123) retained through the study whereas 13.8% (17/123) withdrew from the study. The mean (SD) age was 64 (6.4) years. Overall, 31.7% (39/123) were Hispanics and 24.3% (30/123) were African Americans. The median (IQR) DCI score was 34 (10.3, 68.1) and 30.8% (38/123) of patients belonged to low SES. The median DCI score in participants who retained in the study was statistically similar to those who withdrew from the study (p=0.4). Neither the DCI tiers (p=0.7) nor the low SES (p=0.9) were associated with participants’ retention or withdrawal of the study. In terms of non-adherence, all participants in the withdrawn group had at least one non-adherent event compared to 48.1% in the retained group (p<0.001). Repetitive non-adherence was significantly higher in participants who withdrew from the study vs those who retained in the study [88.2% vs 16.9%, p <0.001]. On multivariate logistic regression analysis, the number of non-adherences (OR=12.5, p<0.001) and not DCI (OR=0.99, p=0.7) appeared to be an independent predictor for participants’ retention or withdrawal from the study.ConclusionsExpanding diverse inclusion and limiting withdrawal with real-time non-adherence monitoring will lead to more efficient clinical research and greater generalizability of results.

Real-World Outcomes for Patients with Relapsed or Refractory (R/R) Aggressive B-Cell Non-Hodgkin's Lymphoma (aBNHL) Treated with Commercial Tisagenlecleucel: Subgroup Analyses from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry

Background: Tisagenlecleucel is an autologous CD19-directed T-cell immunotherapy that provides high rates of durable response, with a manageable safety profile, in adult patients with R/R diffuse large B-cell lymphoma (DLBCL). An overall response rate (ORR) of 53% and progression-free survival (PFS) rate of 33% at 24 months were observed in the pivotal Phase II trial, JULIET (NCT02445248) [Schuster et al. Lancet Oncol 2021; Jaeger et al. Blood 2020]. CIBMTR registry data revealed similar efficacy and a more favorable safety profile for patients with aBNHL treated with tisagenlecleucel in the commercial setting [Landsburg et al.Blood 2021]. The analyses presented here feature a larger cohort with longer follow-up, with outcomes analyzed by pre-infusion clinicopathologic and treatment characteristics. Methods: This non-interventional prospective study used data from the CIBMTR registry and included adult patients with R/R aBNHL in the USA, Canada, and Israel who received commercial tisagenlecleucel after August 30, 2017. Patients were stratified by eligibility for JULIET based on characteristics reported in the registry, such as disease histology, ECOG performance status (PS), comorbidities (recorded as pulmonary, cardiac, renal, or hepatic), and disease status at infusion. Outcomes were assessed in subgroups by reason for JULIET ineligibility, and by lactate dehydrogenase (LDH) level and lymphodepleting chemotherapy (LDC) regimen. LDH was taken as the last known value prior to LDC, or prior to infusion for patients who did not receive LDC. The safety and efficacy sets comprised patients who completed Day 100 safety and efficacy forms, respectively, including those who died prior to Day 100. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT criteria. Results: As of May 4, 2022, data were collected from 1159 patients who received commercial tisagenlecleucel; the median manufacturing turnaround time was 26 days (IQR 24-30). Median age was 67.1 years, 61.2% were male, and 80% had DLBCL. There were 361 JULIET-eligible patients, 641 JULIET-ineligible patients, and 157 patients whose eligibility status could not be defined due to missing data. In the efficacy set (N=968), over a median follow-up of 23.2 months (range: 3.1-46.4), the ORR was 59.5% (Table 1). Month 24 outcomes were 28.4% for PFS, 52.6% for duration of response, and 43.6% for overall survival (OS). Patients with normal versus elevated LDH had improved efficacy outcomes (Table 2), while type of LDC regimen did not appear to impact efficacy (Table 2). Considering individual reasons for JULIET ineligibility, patients in morphologic complete response (CR) at infusion had higher ORR (87.3%) and 24-month PFS (46.3%) and OS (66.1%) than JULIET-eligible patients (Table 1). In patients with ECOG PS ≥2, as well as those with comorbidities (including pulmonary, cardiac, and hepatic disease), PFS was comparable with the JULIET-eligible population (Table 1). In the safety set (N=990), grade ≥3 CRS and ICANS occurred in 6.0% and 7.4% of patients, respectively. Compared with JULIET-eligible patients, rates of CRS and ICANS were lower for patients in morphologic CR at infusion, and higher among those with ECOG PS ≥2. Rates of grade ≥3 CRS were similar between patients with comorbidities and the JULIET-eligible population (Table 1). Conclusions: These analyses using data reported to the CIBMTR, with 1159 patients and >20 months' median follow-up, confirm that real-world outcomes with tisagenlecleucel are broadly similar to those observed in JULIET. Among all patients, normal LDH pre-infusion, but not LDC regimen received, was associated with significantly improved efficacy outcomes. Patients with comorbidities that would have rendered them ineligible for JULIET had similar efficacy outcomes to JULIET-eligible patients. Additionally, efficacy outcomes were similar in patients ineligible for JULIET due to ECOG PS ≥2, albeit with higher rates of grade ≥3 CRS and ICANS. A significantly higher response rate and trend towards improved survival outcomes were observed among patients in morphologic CR before infusion. These data suggest that tisagenlecleucel is appropriate therapy for several subsets of patients who would have been ineligible for JULIET. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Treatment of Immune Thrombocytopenia (ITP) with Eltrombopag - Results of the 5th Interim Analysis of the Study RISA, with Special Consideration of Treatment Discontinuations

Background: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia due to increased platelet clearance and decreased megakaryopoiesis. Eltrombopag (EPAG) is an oral thrombopoietin-receptor agonist, which is proved to be effective and safe in the treatment of ITP. Here we present data from the 5th interim analysis of the RISA study, specially considering the reasons for treatment discontinuation and possible links to the safety profile of EPAG. Methods: RISA is a prospective multicenter non-interventional study in Germany. It started in December 2015, and it will continue until December 2023. Statistical analysis is solely descriptive. Results: Data cutoff for this 5th interim analysis was 11th Feb 2022. 313 patients with persistent or chronic primary ITP (pITP) were enrolled. 302 of them received at least one dose of EPAG and completed at least one post baseline visit. Mean duration of participation was 74.1 months. Mean±SD age was 62.8±17.4 years. 54.8% of the patients were female. Mean±SD duration of ITP at baseline was 5.4±7.5 years. Comorbidity was present in 245 (81.1%) patients. Mean±SD number of concomitant diseases was 2.9±3.0. 99 (32.8%) patients completed the entire treatment period of 24 months, which includes all scheduled visits before data cutoff. Median treatment duration was 14 months (minimum 1 day, maximum 6.1 years). Treatment with EPAG was carried out at a median dosage of 50 mg daily. Median platelet counts increased from baseline 34.0x109/L (N=292) to 91.5x109/L (N=262) within one month. From then and until the end of the two-year observation period, platelet counts remained stable above 90x109/L. The proportion of patients whose platelet count was at least 50x109/L increased from 30.1% at baseline to 74.4% after one month and to 85.6% after twelve months. The number of bleeding events per patient-year decreased, from 1.35 at baseline to 0.59 and 0.16 after one and two years, respectively. 128 (42%) patients discontinued treatment, 51 (40%) of them before day 92. Reasons for discontinuation (multiple answers possible) were insufficient effectiveness in 55 (43%) cases, adverse events (AE) in 36 (28%) cases, death in 20 (16%) cases, non-compliance in 16 (13%) cases, lost to follow up in 10 (8%) cases, cessation of therapy due to complete response in 15 (12%) cases and other reasons in 10 (8%) cases. Across the data set, most frequent AE classified as non-serious adverse drug reactions (nsADR) were fatigue (5.3%), thrombocytopenia (3.3%), thrombocytosis (2.3%), diarrhea (3.0%) and dizziness (2.0%). The most common AE leading to discontinuation of treatment and classified as nsADR were thrombocytosis (1.3%), diarrhea (1.7%), fatigue (1.0%) and arthralgia (1.0%). The most frequent serious AE that led to treatment discontinuation and was rated as serious adverse drug reaction was pulmonary embolism, which occurred in 2 (0.7%) patients. Comorbidity was present in 109 (85.2%) of all patients who discontinued treatment. In this subgroup, the mean±SD number of concomitant diseases was 3.4±3.3. Conclusions: We were able to confirm that EPAG therapy in ITP effectively increases platelet counts and reduces the risk of bleeding. For methodological reasons, we were unable to calculate the actual overall response rate. However, based on the proportion of total patients who were shown to discontinue treatment due to insufficient effectiveness (18%), one could assume that all other patients responded to EPAG at least temporarily. This would result in an overall response rate of 82%. This seems to be consistent with the results of the open extension study EXTEND [Wong RSM et al. Blood 2017; 130: 2527-36], in which a similarly high overall response rate (86%) was found. In general, treatment with EPAG was well tolerated, with no new safety signals from our data set. In view of the high discontinuation rate, it should be borne in mind that about one in eight (12%) of these patients responded so well to EPAG therapy that this was taken as an opportunity for a discontinuation attempt. Other factors that may have contributed to treatment discontinuation included age and comorbidity of patients. Notably, the percentage and number of comorbidities in the discontinuation subgroup were even higher than in the overall study population. However, since this is a non-interventional observational study, results are descriptive and need to be interpreted with caution.

Real-World Efficacy and Safety of Venetoclax Alone and in Combination with Rituximab in Patients with Chronic Lymphocytic Leukemia: Interim Results of the Verone Study

Introduction: The efficacy and tolerability of venetoclax (VEN), a first-in-class selective oral B-cell lymphoma 2 (BCL-2) inhibitor, in patients with chronic lymphocytic leukemia (CLL) have been demonstrated in several clinical trials. This French observational ongoing study aims to describe the effectiveness and tolerability of VEN in routine clinical practice, either as monotherapy or in combination with rituximab. Methods: VERONE is an ongoing prospective non-interventional study conducted in adult CLL patients having started VEN alone until progression or in combination with rituximab as 2-year fixed treatment duration, with a planned follow-up period of 48 months. This interim analysis was performed 4 years after the first inclusion in the study. In each group of patients [monotherapy (VEN) or combination with rituximab (VEN+R)] with at least one follow-up visit (evaluable populations), the best overall response rate (BORR) [proportion of responders, i.e., complete response (CR), CR with incomplete bone marrow recovery, nodular partial response, clinical complete response, or partial response, according to physician's assessment] was estimated at 1 and 2 years after initiation of VEN therapy, as well as progression-free survival (PFS) and overall survival (OS).The primary objective of this study is to describe the effectiveness of venetoclax in terms of best response to treatment up to 12 months. Results: From March 2018 to March 2022, among the 345 analyzed patients included in 64 centres, 227 were retained in the VEN safety population, 94 in the VEN+R safety population, and 13 patients received an other combination than VEN+R. Among the 227 VEN and 94 VEN+R patients, 225 and 94, respectively met all the selection criteria (analyzed populations), and 121 and 70, respectively entered the evaluable populations. In the analyzed populations, respective baseline patient characteristics were as follows: median age, 74.0 (41.0; 91.0) and 73.0 (50.0; 90.0) years; male, 68.6% and 67.0%; ECOG ≥2, 15.6% and 15.5%; del(17p) and/or TP53 mutation, 40.9% and 42.4%; median CLL duration, 8.4 and 8.8 years; median prior lines of therapy, 2 [1;9] and 1 [1;8]; prior B-cell receptor inhibitors 68.0% and 44.7%. In the 121 patients of the VEN evaluable population, the median follow-up duration was 28.4 months at the time of this analysis. It was 24.3 months in the 70 patients of the VEN+R evaluable population. BORR for VEN and VEN+R cohorts are presented in Table 1. In VEN and VEN+R evaluable patients, 1-year PFS were estimated at 84.6% (95% CI [76.3; 90.1]) and 87.2% [76.0; 93.4], respectively; PFS estimates were 71.7% [60.6; 80.2] and 77.9% [64.9; 86.6] at 2 years. Respective 1-year OS were estimated at 88.8% [81.5; 93.4] and 92.9% [83.7; 97.0]; 2-year OS estimates were 79.6% [70.2; 86.3] and 80.6% [68.0; 88.7]. Among both safety populations, 202 VEN patients (89.0%) and 94 VEN+R patients (100%) completed the ramp-up period, and 76.2% and 90.4%, respectively reached the recommended daily dose of 400 mg at the time of analysis. Median durations of treatment were 17.1 and 21.1 months, respectively. Overall, 80.6% and 92.6% of patients, respectively experienced adverse events (AEs), 62.1% and 67.0% ≥grade 3 AEs, 45.8% and 45.7% serious AEs (SAEs), and 18.5% and 17.0% venetoclax-related SAEs (neutropenia 7.0% and 5.3%). Four fatal venetoclax-related AEs were reported in 3 VEN patients (deterioration of the general status, ascites and hepatic failure, death with no precision). Over the ramp-up period, 20 VEN patients (8.8%) and 9 VEN+R patients (9.6%) experienced tumor lysis syndrome which led to treatment discontinuation in 4 (1.8%) and 1 (1.1%) patients. Conclusion: Our interim real-life data tend to confirm that venetoclax used as monotherapy or combination with rituximab is effective in non-selected pre-treated CLL patients, as previously shown in clinical trials. Safety data are reassuring, with no new safety signals identified. BORR seem to be equivalent between each groups of patients and further results are expected next year once survival outcomes are more mature. Table 1: BORR at 1 year and 2 years for VEN and VEN+R cohorts Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Non-Myelofibrosis Chronic Myeloproliferative Neoplasm Patients Show Better Seroconversion Rates after SARS-CoV-2 Vaccination Compared to Other Hematologic Diseases: A Multicentric Prospective Study of KroHem.

Disease- and treatment-mediated immunodeficiency might render SARS-CoV-2 vaccines less effective in patients with hematologic diseases. We performed a prospective non-interventional study to evaluate humoral response after one and two doses of mRNA-1273, BNT162b2, or ChAdOx1 nCoV-19 vaccine in 118 patients with different malignant or non-malignant hematologic diseases from three Croatian treatment centers. An electrochemiluminescent assay was used to measure total anti-SARS-CoV-2 S-RBD antibody titers. After one vaccine dose, 20/66 (33%) achieved seropositivity with a median antibody titer of 6.1 U/mL. The response rate (58/90, 64.4%) and median antibody titer (&gt;250 U/mL) were higher after two doses. Seropositivity varied with diagnosis (overall p &lt; 0.001), with the lowest rates in lymphoma (34.6%) and chronic lymphocytic leukemia (52.5%). The overall response rate in chronic myeloproliferative neoplasms (CMPN) was 81.3% but reached 100% in chronic myeloid leukemia and other non-myelofibrosis CMPN. At univariable analysis, age &gt; 67 years, non-Hodgkin's lymphoma, active treatment, and anti-CD20 monoclonal antibody therapy increased the likelihood of no vaccine response, while hematopoietic stem cell recipients were more likely to respond. Age and anti-CD20 monoclonal antibody therapy remained associated with no response in a multivariable model. Patients with the hematologic disease have attenuated responses to SARS-CoV-2 vaccines, and significant variations in different disease subgroups warrant an individualized approach.

Validation en consultation spécialisée d’un autotest identifiant les patients allergiques aux acariens de la poussière de maison

The increase in the prevalence of allergies in recent decades and the numerous negative repercussions of late treatment lead us to look for more efficient diagnostic methods. House dust mite allergy accounts for more than 75% of paediatric respiratory allergies. The objective of this study is to validate in specialized consultation the new self-test of the brand ExAller to identify subjects allergic to house dust mites and to set up an adequate care. A prospective non-interventional study was carried out in 2020 on a Belgian population of 40 patients aged 3 years and 2 months to 18 years and 10 months. Upstream, we explained the principle of the self-test and obtained the informed consent of the parents. Each patient underwent an anamnesis to assess the likelihood of house dust mite allergy. Patients also underwent skin allergy tests using the prick test method, biology with specific immunoglobulins E to house dust mites Dermatophagoides pteronyssinus and farinae and the self-test. The self-test was compared to the results of the skin prick tests and specific immunoglobulins E. The self-test has a sensitivity of 93.3% and a specificity of 100%. This allows to validate in vivo the new ExAller self-test and to make it available to subjects potentially allergic to house dust mites.