[Clinical Efficacy of Dasatinib, Nilotinib and Imatinib in Newly Diagnosed Patients with Chronic-Phase Chronic Myeloid Leukemia: A Three-year Retrospective Analysis].
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To evaluate efficacy and safety of second-generation tyrosine kinase inhibitors (TKI) dasatinib, nilotinib and imatinib in treatment of newly diagnosed patients with chronic-phase chronic myeloid leukemia (CML).The clinical data and follow-up results of 163 patients with chronic-phase chronic myeloid lenkemia(CP-CML) who were treated in our hospital during the nearly 3 years were analysed retrospectively, among 163 patients 47 received dasatinib, 43 received nilotinib and 73 received imatinib. The efficacy, disease progression and safety were evaluated.After treatment for 3 months, the rate of complete hematologic response(CHR) in three treatment groups were 77%, 79% and 67%, respectivily, CHR at 12 months in three treatment groups were 92%, 91% and 90%, respectively. By 3 months, the rates of complete cytogenetic response(CCyR) with dasatinib and nilotinib were higher than that with imatinib (55%, 53% vs 33%)(P<0.05 for both comparisons), CCyR at 12 months in three treatment groups were 86%, 88% vs 69% (P<0.05 for both comparisons). The rates of major molecular response(MMR) for dasatinib (11%) and nilotinib (9%) by 3 months were significantly higher than that for imatinib (1%) (P<0.05 for both comparisons), MMR at 12 months in three treatment groups were 49%, 50% and 28%, respectively (P<0.05 for both comparison). Progression to the accelerated or blast phase of CML occurred in 2 (4%) patients received dasatinib, 2 (5%) received nilotinib and 6 (8%) received imatinib. The safety profiles of these 3 second-generation TKI treatments were similar.Both dasatinib and nilotinib induced strikingly higher and faster rates of complete cytogenetic response and major molecular response, with a statistically significant difference from imatinib.Keywords:
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Background
Nilotinib is a BCR-ABL inhibitor designed to be more potent and selective than imatinib. Imatinib was the first of a new class of drugs that act by specifically inhibiting a tyrosine kinase receptor.Purpose
To assess the molecular response at 12 months from the start of nilotinib treatment, defined as BCR-ABL transcript levels on the International Scale of 0·1% or less by real-time quantitative PCR in a peripheral blood sample.Materials and Methods
We present data from the ENESTnd study. In ENESTnd, a phase 3, multicentre, open-label, randomised study, patients treated with nilotinib demonstrated higher and faster rates of major molecular response (MMR), more profound molecular response (MR), and complete cytogenetic responses (CCyR) compared with imatinib by 12 and 24 months. 282 adult patients were randomly assigned to receive nilotinib 300 mg twice daily, 281 to receive nilotinib 400 mg twice daily and 283 to receive imatinib. Patients were eligible if they had been diagnosed with chronic phase, Philadelphia chromosome-positive CML within the previous 6 months.Results
By 24 months after the start of treatment, significantly more patients had a MMR with nilotinib than with imatinib (201 with nilotinib 300 mg twice daily, 187 with nilotinib 400 mg twice daily and 124 with imatinib; p < 0.0001 for both comparisons). Significantly more patients in the nilotinib groups achieved a complete molecular response at any time than did those in the imatinib group (74 with nilotinib 300 mg twice daily, 59 with nilotinib 400 mg twice daily and 29 with imatinib; p < 0·0001 for nilotinib 300 mg twice daily vs. imatinib, p = 0.0004 for nilotinib 400 mg twice daily vs. imatinib).Conclusions
Nilotinib continues to demonstrate superiority vs. imatinib with faster and more profound molecular responses. These results support nilotinib as a first-line treatment option for patients with newly diagnosed Philadelphia chromosome-positive and chronic myeloid leukaemia. No conflict of interest.Imatinib Mesylate
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Purpose We report the 5-year analysis from the phase III Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients (DASISION) trial, evaluating long-term efficacy and safety outcomes of patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with dasatinib or imatinib. Patients and Methods Patients with newly diagnosed CML-CP were randomly assigned to receive dasatinib 100 mg once daily (n = 259) or imatinib 400 mg once daily (n = 260). Results At the time of study closure, 61% and 63% of dasatinib- and imatinib-treated patients remained on initial therapy, respectively. Cumulative rates of major molecular response and molecular responses with a 4.0- or 4.5-log reduction in BCR-ABL1 transcripts from baseline by 5 years remained statistically significantly higher for dasatinib compared with imatinib. Rates for progression-free and overall survival at 5 years remained high and similar across treatment arms. In patients who achieved BCR-ABL1 ≤ 10% at 3 months (dasatinib, 84%; imatinib, 64%), improvements in progression-free and overall survival and lower rates of transformation to accelerated/blast phase were reported compared with patients with BCR-ABL1 greater than 10% at 3 months. Transformation to accelerated/blast phase occurred in 5% and 7% of patients in the dasatinib and imatinib arms, respectively. Fifteen dasatinib-treated and 19 imatinib-treated patients had BCR-ABL1 mutations identified at discontinuation. There were no new or unexpected adverse events identified in either treatment arm, and pleural effusion was the only drug-related, nonhematologic adverse event reported more frequently with dasatinib (28% v 0.8% with imatinib). First occurrences of pleural effusion were reported with dasatinib, with the highest incidence in year 1. Arterial ischemic events were uncommon in both treatment arms. Conclusion These final results from the DASISION trial continue to support dasatinib 100 mg once daily as a safe and effective first-line therapy for the long-term treatment of CML-CP.
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Nilotinib is a second-generation tyrosine kinase inhibitor 30-fold more potent than imatinib, with high affinity and selectivity on breakpoint cluster region/V-abl Abelson murine leukemia viral oncogene homolog 1, and also active against a wide range of mutant clones. Phase II trials of nilotinib showed high activity in imatinib-resistant or -intolerant chronic myeloid leukemia patients. Recently, the results of nilotinib as frontline treatment showed high efficacy and superiority as compared with imatinib. Two independent Phase II trials (Italian Group for Adult Hematologic Diseases [GIMEMA] and MD Anderson Cancer Center [MDACC] experiences), testing nilotinib as single agent at standard dose in newly diagnosed patients, showed high rate of cytogenetic and molecular responses with few cases of disease progression. The Phase III randomized Evaluating Nilotinib Efficacy and Safety in Clinical Trials – newly diagnosed patients (ENESTnd) study results demonstrated higher cytogenetic and molecular responses after 24 months (overall major molecular response rate, 62% for nilotinib 300 mg twice daily, 59% for nilotinib 400 mg twice daily compared with 37% for imatinib; overall best complete cytogenetic response rate, 87% for nilotinib 300 mg twice daily, 85% for nilotinib 400 mg twice daily compared with 77% with imatinib), lower rate of progression compared with imatinib (0.7% for nilotinib 300 mg twice daily, 1.1% for nilotinib 400 mg twice daily and 4.2% with imatinib). This article provides substantial evidence on the efficacy and relative tolerability of nilotinib in the management of early chronic phase chronic myeloid leukemia patients.
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Background and Objectives: Chronic myeloid leukemia (CML) accounts for approximately 15% of newly diagnosed cases of leukemia in adults. In this study, the efficacy of nilotinib at 400 mg BID is compared with imatinib at 400 mg BID in CML patients with suboptimal molecular response after at least 12 months of daily dose 400 mg of imatinib therapy. Patients and Methods: This study included a total number of 50 patients, divided into two groups (25 patients each). The first group (Group I): Patients received imatinib at 400 mg BID, second group (Group II): Patients had a suboptimal molecular response to imatinib and received nilotinib at 400 mg BID in early chronic phase. During the two years period of data collection, the primary end included median survival. The secondary end included response rate, type of response, duration of response and progression free survival. Also side effects were recorded. Patients were followed up every month by complete and differential blood counts, liver function test, renal function test and (PCR) every three months for two year. Results: Nilotinib group had significantly higher frequency of major molecular response (MMR) where 23 (92%) patients achieved it while only 16 (64%) patients in Imatinib group achieved MMR (P = 0.01). Nilotinib had better toxicities profile than Imatinib. Conclusion: Both Nilotinib and high dose Imatinib achieved response in CML patients with suboptimal response with rapid and deeper molecular response, better survival outcomes and less side effects in nilotinib.
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