BACKGROUND: Tyrosine kinase inhibitors (TKIs) are the standard of care for adult and pediatric patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP). In adults, 5 TKIs are approved: ...imatinib, dasatinib, nilotinib, bosutinib and ponatinib. In the pediatric population, however, only imatinib, dasatinib and nilotinib are approved. Pediatric pts have similar cytogenetic and molecular response rates to first-line (1L) imatinib and 1L second-generation TKIs nilotinib and dasatinib as adults. While the safety profiles for TKIs are similar in adult and pediatric pts, growth retardation has been reported specifically in the pediatric population. Therefore, safer and more efficacious options are needed for pediatric pts. Asciminib is an investigational drug that inhibits BCR-ABL1 by specifically targeting the ABL myristoyl pocket (STAMP inhibitor). Asciminib has shown promising efficacy and safety in adults with CML-CP in phase I-III trials, given without food for 1 hour prior and 2 hours after taking asciminib (fasted). In the phase I asciminib monotherapy trial in heavily pretreated adult pts, 48% and 28% without and with T315I mutations, respectively, achieved or maintained major molecular response (MMR) by 12 months. In the phase III ASCEMBL trial for adults with CML-CP who are resistant to or intolerant of ≥2 TKIs, 25.5% of pts on asciminib vs 13.2% of pts on bosutinib achieved MMR at 24 weeks. Here we present the phase Ib/II trial evaluating asciminib monotherapy in pediatric pts.
OBJECTIVE: The primary objectives of this study are to characterize the pharmacokinetic (PK) profile of asciminib in pediatric pts and identify a pediatric formulation dose (taken with food) leading to an asciminib exposure comparable to that of 40 mg twice daily (BID) in adult pts (fasted).
DESIGN: This is a multicenter, open-label, phase Ib/II study (NCT04925479, Figure 1). Eligible pts have Philadelphia chromosome-positive CML-CP resistant to or intolerant of ≥1 prior TKI, do not bear T315I mutations and are aged ≥1 to <18 years. Adolescent pts aged ≥14 to <18 years and weighing ≥40 kg will be enrolled in the exploratory adult formulation group, receiving 40 mg asciminib BID in the fasted state until the pediatric formulation is available. There is no prespecified sample size for this group.
In part 1 (dose-determining cohort), 4 to 6 pts aged ≥1 to <18 years will receive the pediatric formulation (body weight-adjusted dose of asciminib minitablets taken with food) to obtain ≥4 participants evaluable for PK data. This evaluation will determine whether median exposure in pediatric pts is comparable to that of asciminib 40 mg BID in adult pts (fasted). Dose adjustments will be made if the minimum exposure is less than that of 20 mg BID in adults or higher than double the maximum exposure in adults at 40 mg BID. During the first 28 days after treatment initiation, safety will be assessed based on predefined dose-limiting toxicities.
In part 2 (expansion cohort), the body weight-adjusted dosing determined in part 1 will be used, and the total pts enrolled on pediatric formulation will be increased to 30, including those from part 1 (15 pts aged 1 to <12 years and 15 pts aged 12 to <18 years). Pts receiving the adult formulation will have the opportunity to switch to the pediatric formulation in part 2 but will not be counted toward the 30 pts enrolled in part 2. A second interim PK and safety analysis will be conducted after all pts in part 2 have completed 28 days of treatment (Figure 2).
The total duration of the study treatment period is 5 years. The primary analysis (primary PK endpoints, safety, and pharmacodynamics) will be assessed after all pts have been on study for 52 weeks or discontinued earlier. A final analysis will be completed after all pts have been on study for 5 years or discontinued earlier. Pts who discontinue the study early will be followed up for survival until the study is complete.
MAIN OUTCOMES MEASURES: The primary endpoints include PK parameters. Secondary endpoints include treatment-associated AEs, hematologic and molecular responses, and acceptability and palatability of asciminib (Table 1).
CONCLUSIONS: Data from this study will be used to support a strategy of full extrapolation from adult data to use in the pediatric setting.
This study is sponsored by Novartis.
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Hijiya: Novartis: Consultancy; Stemline Therapeutics: Consultancy. Kapoor: Novartis: Current Employment, Current equity holder in publicly-traded company. Descamps: Novartis: Current Employment. Bayar: Novartis: Current Employment. Ramscar: Novartis: Current Employment.
Background: Sickle cell disease (SCD) comprises a group of inherited blood disorders, and is a complex, multi-system, disease. SCD is associated with a variety of clinical complications that affect ...multiple organ systems. These complications are driven primarily by vaso-occlusion and hemolytic anemia, and can result in end-organ damage and early death. Painful vaso-occlusive crises (VOCs) are a characteristic feature of SCD and can require healthcare intervention. Despite recent advances in the screening, management and treatment of SCD, gaps remain in our understanding of the disease in the real-world setting. These include how best to transition from pediatric to adult care and how to manage specific complications.
Currently, most real-world evidence (RWE) is generated from information captured in payer databases, which is not as comprehensive as the information recorded in electronic medical records (EMRs). Despite being potentially valuable sources of real-world, clinical information, EMRs for individual patients in the USA are not centralized, often being held by multiple healthcare providers using different EMRs. This fragmented system prevents generation of clear, comprehensive RWE, both in general and for SCD specifically. Furthermore, there is a lack of harmonization between EMR companies/systems in the types of information included and how it's recorded. A separate approach that collates all available data from EMRs into a single, comprehensive record prior to RWE analysis would therefore greatly improve the accessibility of the available information and the quality of subsequent data analysis.
Aims: In contrast to existing RWE, this study explores the value of collating EMRs for each patient into a single, consistently structured format, with the aim of developing richer RWE to complement existing data on SCD. It is hypothesized that the resulting longitudinal overview of each patient's care will contribute to an improved understanding of SCD in the real-world setting: firstly, by better capturing how many VOCs patients with SCD experience, with an indication of the proportion of VOCs that are being home-managed; secondly, by gaining deeper insights into the prevalence and progression of end-organ damage and any association with VOCs; and finally, by highlighting the type and site of care of SCD in the real world (eg medications, treating healthcare professional HCP specialties and the type of clinic visited).
Study design: The study population will comprise 400 patients with SCD from the USA. Patient recruitment occurs directly via social media and indirectly through a variety of partnerships including HCPs and patient advocacy groups. To enroll, patients sign an informed consent form allowing their de-identified medical information to be shared with third-party organizations to advance SCD research. Enrolled patients gain access to their medical records via a dashboard. The key inclusion criteria are: a confirmed SCD diagnosis (irrespective of phenotype); aged ≥16 years at enrollment; and ≥1 inpatient admission for a VOC in the 12 months prior to enrollment. The key exclusion criterion is the absence of medical records. Components of EMRs collected include doctors’ notes, laboratory and test results, clinical imaging and treatment records. Human-curated natural language processing and machine learning is used to extract, structure and code data from the structured sections and unstructured narrative text of the EMR. All medical records, from all visits, will be collected where possible and are expected to comprise ≥7 years of retrospective data for each patient.
Results: Between 1 December 2019 and 24 June 2020, a total of 46 patients with a mean age of 36 years (SD 9.7) were enrolled. For each patient, a median of 6.8 years of data from a median of 32.5 providers were obtained.
Conclusions: The evidence derived from this study aims to advance the understanding of real-world practices in the management of SCD. It may also provide further learnings regarding the prevalence of complications and any association between VOCs and end-organ damage. Generating a single, structured overview of all EMRs for each patient allows for richer insight generation and a more comprehensive analysis of RWE, compared with existing approaches. The insights gained from this RWE may inform future studies and clinical trials in SCD, with the ultimate aim of improving the quality of life of patients.
Clay:Novartis: Consultancy; GBT: Consultancy. Bailey:Novartis Pharmaceuticals Corporation: Current Employment. Drozd:F. Hoffmann-La Roche Ltd: Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.; PicnicHealth: Current Employment, Current equity holder in private company. Paulose:Novartis Pharma AG: Current Employment. Ramscar:Novartis Pharma AG: Current Employment. Mace:Roche/Genentech: Ended employment in the past 24 months; PicnicHealth: Current Employment. Wormser:Novartis Pharma AG: Current Employment, Current equity holder in publicly-traded company.
Sickle cell disease (SCD) is a genetic disorder, characterized by hemolytic anemia and vaso‐occlusive crises (VOCs). Data on the global SCD impact on quality of life (QoL) from the patient viewpoint ...are limited. The international Sickle Cell World Assessment Survey (SWAY) aimed to provide insights into patient‐reported impact of SCD on QoL. This cross‐sectional survey of SCD patients enrolled by healthcare professionals and advocacy groups assessed disease impact on daily life, education and work, symptoms, treatment goals, and disease management. Opinions were captured using a Likert scale of 1‐7 for some questions; 5‐7 indicated “high severity/impact.” Two thousand one hundred and forty five patients (mean age 24.7 years standard deviation (SD) = 13.1, 39% ≤18 years, 52% female) were surveyed from 16 countries (six geographical regions). A substantial proportion of patients reported that SCD caused a high negative impact on emotions (60%) and school achievement (51%) and a reduction in work hours (53%). A mean of 5.3 VOCs (SD = 6.8) was reported over the 12 months prior to survey (median 3.0 interquartile range 2.0‐6.0); 24% were managed at home and 76% required healthcare services. Other than VOCs, fatigue was the most commonly reported symptom in the month before survey (65%), graded “high severity” by 67% of patients. Depression and anxiety were reported by 39% and 38% of patients, respectively. The most common patient treatment goal was improving QoL (55%). Findings from SWAY reaffirm that SCD confers a significant burden on patients, epitomized by the high impact on patientsʼ QoL and emotional wellbeing, and the high prevalence of self‐reported VOCs and other symptoms.
Background: Recent evidence suggests that in patients with immune thrombocytopenia (ITP) with a stable response on thrombopoietin receptor agonists, treatment may be tapered and/or discontinued. ...Objectives: The objective of this study was to provide a guide for tapering and discontinuation of TPO-RA therapy in patients with ITP, based on hematologist survey results, existing evidence, and expert consensus. Patients/Methods: UK hematologists completed a survey to characterize self-reported practice patterns related to TPO-RA tapering and discontinuation in patients with ITP. Using a modified Delphi panel approach, ITP experts developed consensus statements regarding the use of TPO-RA tapering and discontinuation. Results: Survey respondents estimated that 30–34% of their patients were suitable for tapering or discontinuation and that 29–35% of these patients required treatment re-initiation after an average treatment-free interval of 86–106 days. No clear predictors of patient suitability or response to tapering or discontinuation were identified. The ITP expert consensus was that approximately 30% of patients are eligible for tapering and discontinuation, which may be considered after 6–12 months for patients demonstrating an adequate treatment response (platelet count >50,000/µL at ≥75% of assessments in the preceding 6 months). Treatment re-initiation may be considered if the platelet count decreases or if the patient becomes symptomatic. Individual differences need to be taken into account when considering TPO-RA tapering or discontinuation. Conclusions: Tapering and discontinuation of TPO-RA therapy may be considered for certain patients with ITP. Further study is needed to better predict patients likely to achieve sustained off-treatment responses after tapering and discontinuation.
BACKGROUND: Patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) may be treated with 1 of the 4 tyrosine kinase inhibitors (TKIs) approved for first-line (1L) use: ...the first-generation TKI imatinib and the second-generation (2G) TKIs bosutinib, dasatinib, and nilotinib. Deep molecular responses (DMRs) are important criteria for attempting treatment-free remission, an important goal for pts in 1L. However, in 1L, only about 30% of pts treated with imatinib and 30%-55% of pts treated with a 2G TKI achieve MR 4.5 (BCR-ABL1levels on the International Scale≤0.0032%). More than 50% of pts with CML-CP treated with imatinib develop resistance or intolerance to therapy. Among pts treated with a 2G TKI in 1L, 30%-40% need to change therapy by 5 years. Therefore, new treatment options are needed to help pts achieve their treatment goals in 1L.
The main treatment goal for all pts is achievement of disease control, which potentially requires lifelong treatment. Therefore, highly potent, safe treatment options are needed for newly diagnosed pts with CML-CP. Asciminib is an investigational drug that inhibits the BCR-ABL1 oncoprotein through a novel mechanism of action: specifically targeting the ABL myristoyl pocket (STAMP). Due to asciminib's specifically targeting the ABL kinase family (ABL1, ABL2, BCR-ABL1), asciminib monotherapy offers the potential to improve safety and tolerability vs TKIs that target the adenosine triphosphate binding site of BCR-ABL1 and thus have varying degrees of selectivity toward ABL kinases. Asciminib has shown promising efficacy and safety in heavily pretreated adult pts with CML in phase I and III trials. In a phase III trial for pts with CML-CP treated with ≥2 prior TKIs, major molecular response (MMR) was achieved by 25.5% of pts on asciminib (40 mg twice daily BID) vs 13.2% on bosutinib at week 24. In the phase I trial of asciminib monotherapy at doses of 10-200 mg BID and 80-200 mg once daily (QD), 48% of pts with CML-CP treated with ≥2 prior TKIs without T315I mutations achieved or maintained MMR by 12 months. Here we present the upcoming phase III trial evaluating asciminib 80 mg QD monotherapy vs an investigator-selected approved TKI in newly diagnosed adult pts with CML-CP.
OBJECTIVE: The primary objectives of this study are to assess the efficacy of asciminib vs an investigator-selected TKI (either imatinib, bosutinib, dasatinib, or nilotinib) in 1L and to compare the efficacy of asciminib within the stratum receiving investigator-selected imatinib in 1L through the primary end point of MMR rates at week 48. DMRs and; other long-term outcomes are also of interest.
DESIGN: This is a multicenter, open-label, randomized, phase III study of asciminib at 80 mg QD compared with an approved, investigator-selected TKI (either imatinib, bosutinib, dasatinib, or nilotinib) for adult pts with newly diagnosed CML-CP in 1L (expected N=402; NCT04971226). Pts may not have received prior TKI therapy for CML, with the exception of ≤2 weeks of imatinib therapy and must have Eastern Cooperative Oncology Group performance status (ECOG PS) scores of 0 or 1. Pts who have previously received hydroxyurea or anagrelide may be included. Pts will be randomized 1:1 to the asciminib and investigator-selected TKI arms using 2 strata: European Treatment and Outcome Study (EUTOS) long-term survival (ELTS) risk score and the control arm TKI selected by the investigator prior to randomization (Figure 1). Pts randomized to the investigator-selected TKI arm will receive their selected TKIs at approved doses: imatinib, 400 mg QD; bosutinib, 400 mg QD; dasatinib, 100 mg QD; or nilotinib, 300 mg BID.
Pts will remain on study for 5 years after the last pt first treatment has occurred, unless they have discontinued early due to treatment failure, disease progression, intolerance, or investigator or pt decision. Pts who discontinue early will continue to be followed up for survival and disease progression until the end of the study.
MAIN OUTCOMES: The primary end point is MMR at week 48. Key secondary end points include MMR at week 96; exploratory end points include biomarker assessments.
CONCLUSIONS: This study will assess the efficacy of asciminib 80 mg QD in adult pts with newly diagnosed CML-CP vs currently approved TKIs in 1L.
This study is sponsored by Novartis.
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Cortes: Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Astellas, Novartis, Pfizer, Takeda, BioPath Holdings, Incyte: Consultancy, Research Funding; Sun Pharma: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Bio-Path Holdings, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Hochhaus: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding; Incyte: Research Funding. Takahashi: Kyowahakko-Kirin: Research Funding; Ono: Research Funding; Asahikasei: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Eizai: Research Funding; Toyamakagaku: Research Funding; Chugai: Research Funding; Otsuka Pharmaceutical: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Larson: CVS/Caremark: Consultancy; Gilead: Research Funding; Astellas: Consultancy, Research Funding; Rafael Pharmaceuticals: Research Funding; Epizyme: Consultancy; Takeda: Research Funding; Novartis: Research Funding; Cellectis: Research Funding. Issa: Syndax Pharmaceuticals: Research Funding; Kura Oncology: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Bombaci: CML Advocates Network: Consultancy, Current Employment, Membership on an entity's Board of Directors or advisory committees, Other: Organizational Grant Funding; MPN Advocates Network: Membership on an entity's Board of Directors or advisory committees, Other: Organizational Grant Funding; AIL - Associazione Italiana contro le Leucemie, i Linfomi e il Mieloma ONLUS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Organizational Grant Funding; CLL Advocate Network: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Organizational Grant Funding; Novartis: Consultancy, Other: Organizational Grant Funding; Jazz: Consultancy, Other: Organizational Grant Funding; Ceogene: Consultancy, Other: Organizational Grant Funding; Incyte: Consultancy, Other: Organizational Grant Funding; Takeda: Consultancy, Other: Organizational Grant Funding. Ramscar: Novartis: Current Employment. Kapoor: Novartis: Current Employment, Current equity holder in publicly-traded company. Ifrah: Novartis: Current Employment. Hughes: Novartis: Honoraria, Research Funding; BMS: Research Funding; Takeda: Honoraria.
Few studies have reported the real-world use of both romiplostim and eltrombopag in immune thrombocytopenia (ITP). TRAIT was a retrospective observational study aimed to evaluate the platelet ...responses and adverse effects associated with the use of these thrombopoietin receptor agonists (TPO-RAs) in adult patients with ITP in the United Kingdom. Of 267 patients (median age at diagnosis, 48 years) with ITP (primary ITP n = 218, secondary ITP n = 49) included in the study, 112 (42%) received eltrombopag and 155 (58%) received romiplostim as the first prescribed TPO-RA. A platelet count ≥30 × 10
/L was achieved in 89% of patients with the first TPO-RA treatments, while 68% achieved a platelet count ≥100 × 10
/L. Treatment-free response (TFR; platelet count ≥30 × 10
/L, 3 months after discontinuing treatment) was achieved by 18% of the total patients. Overall, 61 patients (23%) switched TPO-RAs, most of whom achieved platelet counts ≥30 × 10
/L with the second TPO-RA (23/25 who switched from eltrombopag to romiplostim 92%; 28/36 who switched from romiplostim to eltrombopag 78%). TFR was associated with secondary ITP, early TPO-RA initiation after diagnosis, the presence of comorbidity and no prior splenectomy or treatment with steroids or mycophenolate mofetil. Both TPO-RAs had similar efficacy and safety profiles to those reported in clinical studies.
OBJECTIVES: Vaso-occlusion is a hallmark feature of sickle cell disease (SCD) that promotes ischemia-reperfusion injury and leads to acute pain episodes, known as vaso-occlusive crises (VOCs). VOCs ...are disabling and frequently impact on the ability of the patient to attend work or school and participate in activities of daily living. VOCs are the primary reason for medical facility visits amongst SCD patients and are associated with increased morbidity and mortality. The acute pain of a VOC often requires parenteral opioid administration in hospital emergency departments and inpatient units. Patients are also frequently prescribed oral opioids to aid in home management of VOCs. The development of new SCD therapies that have been shown to reduce or prevent VOCs has generated interest in their potential as opioid sparing agents. This study evaluated the effect of crizanlizumab-a humanized monoclonal antibody indicated in the US for reduction of VOCs in SCD-on opioid use for managing VOC related pain.
METHODS: In this post hoc analysis, subject-level data from the SUSTAIN (NCT01895361) trial were analyzed to determine the number of days of opioid use by patients in both the 5.0 mg/kg crizanlizumab and placebo arms during the 52-week follow-up period. Opioid use captured in case report forms was retrospectively assessed. Due to the common use of “as needed” (PRN) dosing for analgesics, a decision tree was developed in conjunction with clinical advice to guide classification of the opioid as being taken or not taken on a given day based on clinically plausible assumptions. Assumptions considered dose frequency (fixed vs. PRN), route of administration (parenteral vs. oral), and concomitant medications (anti-emetics and anti-histamines).
Opioid record start dates, end dates, and dose frequencies were used to determine the number of unique days during the trial that each patient had taken at least one opioid. The annualized days with opioid use was calculated for each patient by dividing their number of unique days on opioids by their duration (days) in the trial. The distribution of annualized days with opioid use was compared between patients from the 5.0 mg/kg crizanlizumab and placebo arms. Mann-Whitney U tests with p-values were used to test differences between arms. A four-step analysis was planned to incorporate an increasing number of assumptions to define whether the opioid had been taken on a given day (see footnote of Table 1). Analyses were performed primarily in the per-protocol (PP) population considering all routes of administration and parenteral use only. Outcomes in the intention-to-treat (ITT) population were also assessed.
RESULTS: The PP population included 40 patients in the 5.0 mg/kg crizanlizumab arm and 41 patients in the placebo arm. A comparison of the baseline demographics (age, sex, genotype, hydroxyurea use, crisis frequency, and opioid use) showed no statistically significant differences between the two arms. Results of the final step of each analysis are presented as the primary analysis (see Table 1); results of Step 1 were considered a sensitivity analysis (not shown). The median annualized days with opioid use in the PP population was lower in the crizanlizumab arm compared with the placebo arm (absolute reduction: 4.00 days; relative reduction: 57%; p=0.162). The median annualized days with parenteral opioid use was lower in the crizanlizumab arm compared with the placebo arm (absolute reduction: 2.01; relative reduction: 50%; p=0.047). Results in the ITT population (see Table 1) and for sensitivity analyses (not shown) showed similar trends of reduced annualized days with opioid use for patients in the crizanlizumab group compared to the placebo group.
CONCLUSIONS: These findings indicate that crizanlizumab, compared with placebo, may reduce the annual number of days where opioids are used to manage pain from VOCs. Importantly, the benefit was observed for parenteral and oral opioids, demonstrating clinical and patient relevance. These findings are concordant with the tendency for crizanlizumab to reduce the number of VOCs experienced by SCD patients annually; the primary finding of the SUSTAIN trial. The reduction in opioid use with crizanlizumab requires exploration in future studies, but the findings of this study translate into positive clinical and patient-relevant outcomes beyond reducing the frequency of VOCs.
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Smith:Shire: Research Funding; Imara: Research Funding; Novo Nordisk: Consultancy; Ironwood: Consultancy; Pfizer: Consultancy; Incyte: Other: Investigator; Health Resources and Services Administration: Other: Investigator, Research Funding; Patient-Centered Outcomes Research Institute: Other: Investigator, Research Funding; NHLBI: Research Funding; Shire, Inc.: Other: Investigator, Research Funding; Global Blood Therapeutics, Inc.: Consultancy, Research Funding; Novartis, Inc.: Consultancy, Other: Investigator, Research Funding; Emmaeus Pharmaceuticals, Inc.: Consultancy; GlycoMimetics, Inc.: Consultancy. Ataga:Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire/Takeda: Research Funding; Editas Medicine: Honoraria; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Forma Therapeutics: Consultancy; Modus Therapeutics: Honoraria; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Research Funding. Saraf:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Boards, Speakers Bureau; Novartis, Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pfizer, Global Blood Therapeutics, Novartis: Research Funding. Adisa:Novartis Pharmaceuticals Corporation: Current Employment. Bailey:Novartis Pharmaceuticals Corporation: Current Employment. Ramscar:Novartis Pharma AG: Current Employment. Bonner:Eversana: Current Employment. Brown:Eversana: Current Employment. Pastor:Eversana: Current Employment.
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Thrombopoietin receptor agonists (TRA) have shown efficacy in clinical trials for patients with immune thrombocytopenia (ITP), achieving initial response rates of up to 88%. However, there is ...limited research on the effectiveness of TRA in routine clinical practice. The primary objective of this retrospective, observational study was to describe the proportion of patients who achieve platelet counts plts ≥30,000/µl within 12 weeks of TRA initiation (treatment response; R). Secondary objectives of this study were to assess the safety and tolerability of TRA, the duration of treatment, maintenance of R, whether patients are able to come off treatment (TRA discontinuation) and, whether different treatment responses are observed in primary versus secondary ITP.
Patients aged ≥ 18 years with ITP (primary or secondary) who had initiated TRA (eltrombopag EPG or romiplostim RPM) treatment ≥4 months prior to data collection were included in the study from UK secondary and tertiary care centres. Data on patient characteristics, disease history, TRA treatment pathways, response to treatment and adverse events (AEs) were collected from medical records (observation period from date of ITP diagnosis to data collection).
Overall 267 eligible patients from 15 centres were included (primary ITP n=218, secondary ITP n=49); 42% (n=112/267) and 58% (n=155/267) of patients received EPG and RPM respectively as the first prescribed TRA. The study sample comprised 52% females (n=139/267); median (interquartile range IQR) age at TRA initiation was 56 years (40-70). The median (IQR) time from diagnosis of primary and secondary ITP to first TRA treatment was 4.0 years (0.9-11.7) and 1.9 years (0.2-9.5), respectively. 26% (n=57/ 218) of patients with primary ITP and 46% (n=22/48, no diagnosis date recorded for n=1) of patients with secondary ITP received their first TRA within 1 year of diagnosis.
Proportion of patients achieving and maintaining R, discontinuing treatment and median time to achieve first R for all patients are described in the table below. 23% (n=61/267) of all patients received both TRAs during the observation period, with 10% (n=6/61, n=5 initiated with RPM) patients switching to receive both TRAs at the same time. 23% (n=36/155) of all patients initiated on RPM switched to EPG and 22% (n=25/112) of all patients initiated on EPG switched to RPM.
AEs (related to the use of TRA) were recorded in 33% (n=31/95) and 23% (n=28/123) of patients with primary ITP receiving EPG and RPM respectively. 12% (n=31/267) of all patients discontinued their initial TRA due to poor response (n=20), adverse events (n=7) or complications (n=4). Of the remaining 236 patients, 20% (n=48/236) patients discontinued their initial TRA due to physician/patient request (n=31) or for an unrecorded reason (n=17). 8% (n=14/267) patients discontinued their initial TRA due to reasons other than those listed above and data was unavailable for 2% (n=6/267) patients.
17% (n=36/218) of patients with primary ITP discontinued TRAs within one year of initiation (15% n=14/95 on EPG and 18% n=22/123 RPM). 39% (n=19/49) of patients with secondary ITP discontinued TRA within one year of treatment initiation (47% n=8/17 on EPG and 34% n=11/32 RPM). 67% (n=147/218) of patients with primary ITP and 43% (n=21/49) of patients with secondary ITP were still receiving a TRA at the time of data collection.
Of the 237 patients achieving R, 21% (n=49/236) discontinued TRA treatment within one year of initiation. The median (IQR) time to discontinuation of TRA after achieving R for all patients, was 34 (13 - 97) weeks.
The results from this retrospective observational study suggest that patients with primary and secondary ITP respond to TRA in real world settings in a manner that is consistent with results from clinical trials. These results also show that greater proportions of patients with secondary ITP are able to discontinue TRA treatment within one year of initiation suggesting the benefit of these treatments in ITP patient care.
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Cooper:Amgen, Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Provan:Amgen, Novartis: Honoraria, Research Funding. Scully:Novartis: Honoraria, Other: Member of Advisory Board, Speakers Bureau. Grech:Novartis: Other: sponsorship for scientific meetings. Bagot:Amgen, Novartis: Speakers Bureau. Hill:Novartis: Honoraria; Novartis: Honoraria. Nokes:Bayer, MSD, Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ramscar:Novartis: Employment. Saunders:pH associates: Employment.
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