How we will treat chronic myeloid leukemia in 2016

Talati, Chetasi; Ontiveros, Evelena P.; Griffiths, Elizabeth A.; Wang, Eunice S.; Wetzler, Meir

doi:10.1016/j.blre.2014.12.003

Cited by 13 publications

(12 citation statements)

References 41 publications

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“…Thus, there is the necessity of searching for new targets and personalized therapies (16,37,38). In addition, our data indicate that BGB324 is active in BCR-ABL TKIresistant CML cells and mouse models, including T315I-mutated and ponatinibresistant systemic mouse models and primary cells.…”

Section: Discussionmentioning

confidence: 78%

Axl Blockade by BGB324 Inhibits BCR-ABL Tyrosine Kinase Inhibitor–Sensitive and -Resistant Chronic Myeloid Leukemia

Ben-Batalla

Erdmann

Jørgensen

et al. 2017

Clinical Cancer Research

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Ben Batalla, I. et al. (2017) Axl blockade by BGB324 inhibits BCR-ABL tyrosine kinase inhibitor-sensitive and -resistant chronic myeloid leukemia. Clinical Cancer Research, 23(9), pp. 2289-2300. (doi:10.1158/1078-0432.CCR-16-1930 This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/131767/ STATEMENT OF TRANSLATIONAL RELEVANCEABL tyrosine kinase inhibitors (TKI) are employed for chronic myeloid leukemia (CML) treatment and induce durable remissions in the majority of patients. However, resistant disease and persistence of BCR-ABL1-independent leukemia stem and progenitor cells remain clinical challenges.Furthermore, ABL-TKI are associated with the risk of severe side effects in long term use. Therefore, novel therapeutic strategies are warranted to target persisting stem cells and resistant clones alone or in combination with ABL-TKI.We demonstrate here the activity of an Axl inhibitor, BGB324, against TKI-sensitive and -resistant BCR-ABL1 positive cells, including T315I-mutated and ponatinib-resistant primary cells. Inhibition of Axl with BGB324 exerted therapeutic effects in complementary T315I-mutated and ponatinib-resistant preclinical mouse models. BGB324 was well-tolerated in Phase 1 clinical trials in healthy volunteers and AML patients (BGBC001, BGBC003 ongoing). Thus our findings can be rapidly translated to the clinics and BGB324 holds promise to improve treatment of CML patients.

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Section: Discussionmentioning

confidence: 78%

Axl Blockade by BGB324 Inhibits BCR-ABL Tyrosine Kinase Inhibitor–Sensitive and -Resistant Chronic Myeloid Leukemia

Ben-Batalla

Erdmann

Jørgensen

et al. 2017

Clinical Cancer Research

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“…The risk of death was associated with the advanced phase at the diagnosis, discontinuation of imatinib therapy, and the failure or insufficient response during the treatment with imatinib. Indeed, for patients who fail frontline therapy with imatinib, second-line options must be started including second-and third-generation TKIs [25][26][27], all of which are unavailable in our country. For patients in advanced phase at the diagnosis, Thota et al [28] found that even though imatinib can enable cytogenetic remission, survival remains lower than in patients in chronic phase at diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Pattern of chronic myeloid leukemia in the imatinib era in a Sub-Saharan African setting

et al. 2016

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Chronic myeloid leukemia (CML) is an orphan disease in Africa because of the inaccessibility to specific treatment and the high cost of diagnosis and monitoring patients. The aim of this study was to report CML treatment response in a developing country in the tyrosine kinase inhibitor era. We conducted a longitudinal study of our cohort of CML patients. Socio-demographic, diagnosis, therapeutic, and treatment response parameters were studied. Sokal score, disease phase at diagnosis, delay from diagnosis to treatment, and treatment response were analyzed for their impact on survival. Fifty-five patients with a diagnosis of CML and who received treatment with imatinib for a minimum of 3 months were included in this study. Median follow-up was 170 patient-years. The sex ratio (M/F) was 1.62 and median age at diagnosis was 42 years. At diagnosis, 85.5 % of the patients were in chronic phase (CP), 12.7 % in accelerated phase (AP), and 1.8 % in blast crisis (BC). Sokal risk score distribution was as follows: low risk 29.8 %, intermediate risk 38.3 %, and high risk 31.9 %. Median time from first symptoms to first medical visit was 6.2 months and median time from first medical visit to cytogenetic and or molecular confirmation was 12.4 months. Mean delay time from first medical visit to imatinib initiation was 12.5 months (95 % CI 6.3-18.7). The complete hematologic response (CHR) at 3 months, the major cytogenetic response (MCR) at 12 months, and the major molecular response (MMR) at 24 months were respectively 82.4, 75, and 25 %. The 2-year overall survival rate was 81 %. Advanced phase at the diagnosis, discontinuation of imatinib therapy over 15 % of the time, lack of CHR at 3 months, lack of MCR at 12 months, and progression of the disease during imatinib therapy were associated with a risk of death (p ≤ 0.05). Our data confirm the improved prognosis of CML treated with imatinib in the setting of a developing country. However, response rates are lower than in developed countries, and additional efforts should be made to facilitate early diagnosis and improve access to TKI, treatment compliance, and regular molecular monitoring of patients.

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“…Comparatively, there are fewer NHW ALLs in the 2002–2011 period, which can be caused by changes in both incidence and diagnosis. There are multiple treatment strategies for leukemia 14 , 15 , including induction chemotherapy, consolidation therapy (or intensification therapy), preventive therapy, maintenance treatments with chemotherapeutic drugs, and others. For most cases, radiation is not the mainline treatment, as has been observed in this analysis.…”

Section: Discussionmentioning

confidence: 99%

Racial Differences in Four Leukemia Subtypes: Comprehensive Descriptive Epidemiology

Zhao

Wang

2018

Sci Rep

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Leukemia is a malignant progressive disease and has four major subtypes. Different racial groups differ significantly in multiple aspects. Our goal is to systematically and comprehensively quantify racial differences in leukemia. The SEER database is analyzed, and comprehensive descriptive analysis is provided for the four major subtypes, namely ALL (acute lymphoblastic leukemia), CLL (chronic lymphoblastic leukemia), AML (acute myeloid leukemia), and CML (chronic myeloid leukemia), and for two age groups (≤14 and >14) separately. The racial groups studied include NHW (non-Hispanic White), HW (Hispanic White), BL (Black), and API (Asian and Pacific Islander). Univariate and multivariate analyses are conducted to quantify racial differences in patients’ characteristics, incidence, and survival. For patients’ characteristics, significant racial differences are observed in gender, age at diagnosis, diagnosis era, using radiation for treatment, registry, cancer history, and histology type. For incidence, significant racial differences are observed, and the patterns vary across subtypes, gender, and age groups. For most of the subtypes and gender and age groups, Blacks have the worst five-year survival, and significant racial differences exist. This study provides a comprehensive epidemiologic description of racial differences for the four major leukemia subtypes in the U.S. population.

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How we will treat chronic myeloid leukemia in 2016

Cited by 13 publications

References 41 publications

Axl Blockade by BGB324 Inhibits BCR-ABL Tyrosine Kinase Inhibitor–Sensitive and -Resistant Chronic Myeloid Leukemia

Axl Blockade by BGB324 Inhibits BCR-ABL Tyrosine Kinase Inhibitor–Sensitive and -Resistant Chronic Myeloid Leukemia

Pattern of chronic myeloid leukemia in the imatinib era in a Sub-Saharan African setting

Racial Differences in Four Leukemia Subtypes: Comprehensive Descriptive Epidemiology

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