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Association details:
Evidence:
Evidence Level:
Sensitive: B - Late Trials
New
Source:
Title:

Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations

Excerpt:
Here, dasatinib efficacy was analyzed in patients recruited to phase 2/3 trials with chronic-phase chronic myeloid leukemia with or without BCR-ABL mutations after prior imatinib. High response rates were observed in patients with the majority of different BCR-ABL mutation types, including highly imatinib-resistant mutations in L248, Y253, E255, F359, and H396, in addition to other common mutations in G250 and M351 (Figure 4).
DOI:
10.1182/blood-2009-04-214221
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
New
Source:
Title:

Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase

Excerpt:
Mutations were identified in 60 (60%) of these patients (all with imatinib-resistant CML-AP). Despite the presence of imatinib-resistant BCR-ABL mutations and their association with poor prognosis, at 8 months' follow-up, 73% of patients with an imatinib-resistant BCR-ABL mutation had achieved MaHR following treatment with dasatinib.
DOI:
10.1182/blood-2006-09-046839
Evidence Level:
Sensitive: C3 – Early Trials
New
Title:

Dasatinib in the Treatment of Chronic Myeloid Leukemia in Accelerated Phase After Imatinib Failure: The START A Trial

Excerpt:
Patients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily. The number of patients with BCR-ABL mutations before study treatment was 88 (56%) of 156, and 29 different mutations were detected. As noted previously,17 patients with a preexisting T315I mutation (n = 9) did not respond to dasatinib therapy (Table 3). Few CCyRs were observed in patients with F317L (0 of four) or E255K (one of eight) mutations.
DOI:
10.1200/JCO.2007.14.3339
Trial ID:
Evidence Level:
Sensitive: D – Preclinical
New
Title:

Activity of Bosutinib, Dasatinib, and Nilotinib Against 18 Imatinib-Resistant BCR/ABL Mutants

Excerpt:
CONTRADICTING EVIDENCE: In our study, we investigated the activity of bosutinib, dasatinib, imatinib, and nilotinib against a panel of 18 mutated forms of BCR/ABL associated with imatinib resistance in CML and Ph+ acute lymphoblastic leukemia patients. The results are listed in Figure 1 (Table 1 lists all the actual values for the relative concentration that inhibits 50%).
DOI:
10.1200/JCO.2008.19.8853
Evidence Level:
Sensitive: D – Preclinical
New
Source:
Title:

Overriding Imatinib Resistance with a Novel ABL Kinase Inhibitor

Excerpt:
BMS-354825 is an orally bioavailable ABL kinase inhibitor with two-log increased potency relative to imatinib that retains activity against 14 of 15 imatinib-resistant BCR-ABL mutants. BMS354825 prolongs survival of mice with BCR-ABL– driven disease and inhibits proliferation of BCR-ABL–positive bone marrow progenitor cells from patients with imatinib-sensitive and imatinib-resistant CML....In vitro analysis of cell-growth inhibition of imatinib-resistant Ba/F3 cells expressing the indicated BCR-ABL mutants. Viable cell counts were performed in triplicate after 48 hours of exposure to BMS-354825 and normalized to the dimethyl sulfoxide–treated sample.
DOI:
10.1126/science.1099480