Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Clinical efficacy and safety of imatinib in the management of Ph(+) chronic myeloid or acute lymphoblastic leukemia in Chinese patients.

ABSTRACT: Imatinib mesylate is considered the standard first-line systemic treatment for patients with chronic myeloid leukemia (CML) and functions by targeting BCR-ABL tyrosine kinases. Imatinib has substantially changed the clinical management and improved the prognosis of CML and Philadelphia chromosome-positive acute lymphocytic leukemia (Ph(+) ALL). Here, we review the pharmacology, mode of action, and pharmacokinetics of imatinib; Chinese efficacy studies in CML and Ph(+) ALL; safety and tolerability; patient-focused perspectives, such as quality of life, patient satisfaction, acceptability, and adherence; and uptake of imatinib.

SUBMITTER: Zhu Y

PROVIDER: S-EPMC3949731 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Clinical efficacy and safety of imatinib in the management of Ph(+) chronic myeloid or acute lymphoblastic leukemia in Chinese patients.

Zhu Yu Y Qian Si-Xuan SX

OncoTargets and therapy 20140306

Imatinib mesylate is considered the standard first-line systemic treatment for patients with chronic myeloid leukemia (CML) and functions by targeting BCR-ABL tyrosine kinases. Imatinib has substantially changed the clinical management and improved the prognosis of CML and Philadelphia chromosome-positive acute lymphocytic leukemia (Ph(+) ALL). Here, we review the pharmacology, mode of action, and pharmacokinetics of imatinib; Chinese efficacy studies in CML and Ph(+) ALL; safety and tolerabilit ...[more]

PMID: 24623982

Similar Datasets

Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: Minimum 24-month follow-up.

Project description:Bosutinib is an orally active, dual Src/Abl tyrosine kinase inhibitor for treatment of chronic myeloid leukemia (CML) following resistance/intolerance to prior therapy. Here, we report the data from the 2-year follow-up of a phase 1/2 open-label study evaluating the efficacy and safety of bosutinib as second-line therapy in 288 patients with chronic phase CML resistant (n?=?200) or intolerant (n?=?88) to imatinib. The cumulative response rates to bosutinib were as follows: 85% achieved/maintained complete hematologic response, 59% achieved/maintained major cytogenetic response (including 48% with complete cytogenetic response), and 35% achieved major molecular response. Responses were durable, with 2-year estimates of retaining response >70%. Two-year probabilities of progression-free survival and overall survival were 81% and 91%, respectively. The most common toxicities were primarily gastrointestinal adverse events (diarrhea [84%], nausea [45%], vomiting [37%]), which were primarily mild to moderate, typically transient, and first occurred early during treatment. Thrombocytopenia was the most common grade 3/4 hematologic laboratory abnormality (24%). Outcomes were generally similar among imatinib-resistant and imatinib-intolerant patients and did not differ with age. The longer-term results of the present analysis confirm that bosutinib is an effective and tolerable second-line therapy for patients with imatinib-resistant or imatinib-intolerant chronic phase CML. ClinicalTrials.gov Identifier: NCT00261846.

| S-EPMC4173127 | biostudies-literature

Real-world efficacy and safety outcomes of imatinib treatment in patients with chronic myeloid leukemia: An Australian experience.

Project description:Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of chronic myeloid leukemia (CML), but patients still experience treatment-limiting toxicities or therapeutic failure. To investigate the real-world use and outcomes of imatinib in patients with CML in Australia, a retrospective cohort study of patients with CML commencing imatinib (2001-2018) was conducted across two sites. Prescribing patterns, tolerability outcomes, and survival and molecular response were evaluated. 86 patients received 89 imatinib treatments. Dose modifications were frequently observed (12-month rate of 58%). At last follow-up, 62 patients (5-year rate of 55%) had permanently discontinued imatinib treatment, of which 44 switched to another TKI (5-year rate of 46%). Within 3 months of starting imatinib, 43% (95% CI, 32%-53%) of patients experienced imatinib-related grade ≥3 adverse drug reactions (ADRs). Higher comorbidity score, lower body weight, higher imatinib starting dose, and Middle Eastern or North African ancestry were associated with a higher risk of grade ≥3 ADR occurrence on multivariable analysis (MVA). Estimated overall survival and event-free survival rates at 3 years were 97% (95% CI, 92%-100%) and 81% (95% CI, 72%-92%), respectively. Cumulative incidence of major molecular response (MMR) at 3 years was 63% (95% CI, 50%-73%). On MVA, imatinib starting dose, ELTS score, BCR-ABL1 transcript type, pre-existing pulmonary disease, and potential drug-drug interactions were predictive of MMR. In conclusion, imatinib induced deep molecular responses that translated to good survival outcomes in a real-world setting, but was associated with a higher incidence of ADRs, dose modifications and treatment discontinuations than in clinical trials.

| S-EPMC9475133 | biostudies-literature

Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase.

Project description:BACKGROUND:Imatinib mesylate given orally at a daily dose of 400 mg is the standard of care as initial therapy for patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP). Treatment guidelines propose dose escalation based on clinical assessments of disease response. METHODS:Response and survival were analyzed in a cohort of patients (n = 106) with newly diagnosed CML-CP who were enrolled on the International Randomized Study of Interferon and STI571 (IRIS) trial, who began treatment with imatinib at a dose of 400 mg daily, and who subsequently underwent dose escalation to either 600 mg or 800 mg daily. Reasons for dose escalation were evaluated retrospectively based on 2 sets of criteria: the IRIS protocol-defined criteria (n = 39 patients) and the European LeukemiaNet (ELN) recommendations (n = 48 patients). RESULTS:Among all 106 patients who underwent dose escalation, the rates of freedom from progression to accelerated phase or blast phase and overall survival were 89% and 84% at 3 years after dose increase, respectively. A cytogenetic response was obtained in 42% of patients who had their dose escalated based on protocol criteria and in 38% of patients who had their dose escalated according to the ELN recommendations. CONCLUSIONS:The results from this retrospective analysis supported imatinib dose escalation as an appropriate initial option for patients with CML-CP who were experiencing suboptimal cytogenetic response or resistance.

| S-EPMC4445370 | biostudies-literature

Long-term treatment with imatinib results in profound mast cell deficiency in Ph+ chronic myeloid leukemia.

Project description:Although mast cells (MC) play an important role in allergic reactions, their physiologic role remains unknown. In mice, several models of MC-deficiency have been developed. However, no comparable human model is available. We examined the in vitro- and in vivo effects of the KIT-targeting drug imatinib on growth and development of human MC. Imatinib was found to inhibit stem cell factor (SCF)-induced differentiation of MC in long-term suspension cultures (IC50: 0.01 µM). Correspondingly, long-term treatment of chronic myeloid leukemia (CML) patients with imatinib (400 mg/day) resulted in a marked decrease in MC. In patients with continuous complete molecular response during therapy, bone marrow MC decreased to less than 5% of pre-treatment values, and also serum tryptase concentrations decreased significantly (pre-treatment: 32.0 ± 11.1 ng/ml; post-therapy: 3.4 ± 1.8, p<0.01). Other myeloid lineages, known to develop independently of KIT, were not affected by imatinib-therapy. Imatinib also produced a substantial decrease in MC-development in mice. However, no clinical syndrome attributable to drug-induced MC-deficiency was recorded in our CML patients. Together, imatinib suppresses MC production in vitro and in vivo. However, drug-induced MC depletion is not accompanied by adverse clinical events, suggesting that MC are less relevant to homeostasis in healthy tissues than we assumed so far.

| S-EPMC4413638 | biostudies-literature

Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib.

Project description:Bosutinib, a dual Src/Abl kinase inhibitor, has shown potent activity against chronic myeloid leukemia (CML). In this phase 1/2 study we evaluated bosutinib in patients with chronic phase imatinib-resistant or imatinib-intolerant CML. Part 1 was a dose-escalation study to determine the recommended starting dose for part 2; part 2 evaluated the efficacy and safety of bosutinib 500 mg once-daily dosing. The study enrolled 288 patients with imatinib-resistant (n = 200) or imatinib-intolerant (n = 88) CML and no other previous kinase inhibitor exposure. At 24 weeks, 31% of patients achieved major cytogenetic response (primary end point). After a median follow-up of 24.2 months, 86% of patients achieved complete hematologic remission, 53% had a major cytogenetic response (41% had a complete cytogenetic response), and 64% of those achieving complete cytogenetic response had a major molecular response. At 2 years, progression-free survival was 79%; overall survival at 2 years was 92%. Responses were seen across Bcr-Abl mutants, except T315I. Bosutinib exhibited an acceptable safety profile; the most common treatment-emergent adverse event was mild/moderate, typically self-limiting diarrhea. Grade 3/4 nonhematologic adverse events (> 2% of patients) included diarrhea (9%), rash (9%), and vomiting (3%). These data suggest bosutinib is effective and tolerable in patients with chronic phase imatinib-resistant or imatinib-intolerant CML. This trial was registered at http://www.clinicaltrials.gov as NCT00261846.

| S-EPMC4916618 | biostudies-literature

Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia.

Project description:The development of imatinib for the treatment of chronic myeloid leukemia (CML) has proven to be an example of medical success in the era of targeted therapy. However, imatinib resistance or intolerance occurs in a substantial number of patients. Additionally, patients who have progressed beyond the chronic phase of CML do relatively poorly with imatinib therapy. Mechanisms of imatinib resistance include BCR-ABL point mutations resulting in decreased imatinib binding, as well as mutation-independent causes of resistance such as SRC family kinase dysregulation, BCR-ABL gene amplification, drug influx/efflux mechanisms and other poorly understood processes. The options for therapy in these patients include stem cell transplantation, imatinib dose escalation as well as the use of second-generation tyrosine kinase inhibitors. Dasatinib is a second-generation multi-kinase inhibitor with several theoretical and mechanistic advantages over imatinib. Moreover, several studies have evaluated dasatinib in patients who have progressed on imatinib therapy with encouraging results. Other novel agents such as mTOR inhibitors, bosutinib and INNO 406 have also shown promise in this setting. Although treatment options have increased, the choice of second-line therapy in patients with CML is influenced by concerns surrounding the duration of response as well as toxicity. Consequently, there is no agreed upon optimal second-line agent. This paper reviews the current data and attempts to address these issues.

| S-EPMC2726068 | biostudies-other

Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia.

Project description:BackgroundIn order to improve the molecular response rate and prevent resistance to treatment, combination therapy with different dosages of imatinib and cytarabine was studied in newly diagnosed patients with chronic myeloid leukemia in the HOVON-51 study.Design and methodsHaving reported feasibility previously, we hereby report the efficacy of escalated imatinib (200 mg, 400 mg, 600 mg or 800 mg) in combination with two cycles of intravenous cytarabine (200 mg/m(2) or 1000 mg/m(2) days 1 to 7) in 162 patients with chronic myeloid leukemia.ResultsWith a median follow-up of 55 months, the 5-year cumulative incidences of complete cytogenetic response, major molecular response, and complete molecular response were 89%, 71%, and 53%, respectively. A higher Sokal risk score was inversely associated with complete cytogenetic response (hazard ratio of 0.63; 95% confidence interval, 0.50-0.79, P<0.001). A higher dose of imatinib and a higher dose of cytarabine were associated with increased complete molecular response with hazard ratios of 1.60 (95% confidence interval, 0.96-2.68, P=0.07) and 1.66 (95% confidence interval, 1.02-2.72, P=0.04), respectively. Progression-free survival and overall survival rates at 5 years were 92% and 96%, respectively. Achieving a major molecular response at 1 year was associated with complete absence of progression and a probability of achieving a complete molecular response of 89%.ConclusionsThe addition of intravenous cytarabine to imatinib as upfront therapy for patients with chronic myeloid leukemia is associated with a high rate of complete molecular responses (Clinicaltrials.Gov Identifier: NCT00028847).

| S-EPMC2878788 | biostudies-literature

Tyrosine Kinase Inhibitors Available for Chronic Myeloid Leukemia: Efficacy and Safety.

Project description:Chronic myeloid leukemia (CML) is currently a disease in which patients can enjoy a near normal life-expectancy. However, since the majority of patients will need to remain on treatment indefinitely, physicians in care of CML patients need be familiar with the indications and toxicities of all approved tyrosine kinase inhibitors (TKI). In clinical practice, there are five TKI (imatinib, nilotinib, dasatinib, bosutinib, and ponatinib) that are available in different scenarios and have distinct safety profiles. Decisions regarding first line treatment must be based on CML risk, comorbidities, and patients expectations. Despite the excellent outcome, half of the patients will eventually fail (due to intolerance or resistance) to first line treatment, with many of them requiring a third or even further lines of therapy. When selecting for such patients, it is essential to distinguish between failure and intolerance to previous TKIs. In the present review, we will address all these issues from a practical point of view.

| S-EPMC6617580 | biostudies-literature

Prediction of outcomes in patients with Ph+ chronic myeloid leukemia in chronic phase treated with nilotinib after imatinib resistance/intolerance.

Project description:The purpose was to assess predictive factors for outcome in patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP) treated with nilotinib after imatinib failure. Imatinib-resistant and -intolerant patients with CML-CP (n=321) were treated with nilotinib 400 mg twice daily. Of 19 baseline patient and disease characteristics and two response end points analyzed, 10 independent prognostic factors were associated with progression-free survival (PFS). In the multivariate analysis, major cytogenetic response (MCyR) within 12 months, baseline hemoglobin ? 120 g/l, baseline basophils <4%, and absence of baseline mutations with low sensitivity to nilotinib were associated with PFS. A prognostic score was created to stratify patients into five groups (best group: 0 of 3 unfavorable risk factors and MCyR by 12 months; worst group: 3 of 3 unfavorable risk factors and no MCyR by 12 months). Estimated 24-month PFS rates were 90%, 79%, 67% and 37% for patients with prognostic scores of 0, 1, 2 and 3, respectively, (no patients with score of 4). Even in the presence of poor disease characteristics, nilotinib provided significant clinical benefit in patients with imatinib-resistant or -intolerant CML. This system may yield insight on the prognosis of patients.

| S-EPMC4140185 | biostudies-literature

Efficacy and safety of dasatinib versus imatinib in the East Asian subpopulation of the DASISION trial of newly diagnosed chronic myeloid leukemia in chronic phase.

Project description:Asian patients with chronic myeloid leukemia (CML) tend to have different characteristics compared with patients from other regions, including younger age and smaller body size. The phase 3, open-label, randomized DASISION trial (NCT00481247), comparing dasatinib 100 mg once daily (QD) (n = 259) with imatinib 400 mg QD (n = 260) in newly diagnosed chronic phase CML (CML-CP), included a sizeable East Asian population (n = 60: dasatinib; n = 48: imatinib). In East Asian patients, dasatinib showed favorable 24-month rates of major molecular response (68% vs. 50% for imatinib) and complete cytogenetic response (92% vs. 88%), and more patients achieved BCR-ABL1 transcript levels ≤ 10% at 3 months with dasatinib (91% vs. 69%), similar to the overall population. Relative to non-East Asian patients, the incidence of rash, fluid-related events and grade 3/4 neutropenia and thrombocytopenia appeared to be higher in East Asians, regardless of treatment. Pharmacokinetic analysis revealed statistically non-significant increased dasatinib exposure among East Asian patients. Results support the use of dasatinib 100 mg QD as first-line CML treatment in both East Asian and non-East Asian patients.

| S-EPMC4196520 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data