Revised text to state that at 5 years, there was no difference in progression-free survival (PFS) or overall survival (OS). Added that progression to accelerated-phase CML or blast crisis occurred in 7% of patients on imatinib and in 5% of patients on dasatinib (cited Cortes et al. as reference 8).
Revised text to state that although one of these two studies showed statistically significant decreased rates of progression to accelerated or blastic phase, the 5- to 10-year follow-up period with nilotinib and dasatinib demonstrated a survival for these agents similar to that for imatinib.
Revised text to state that allogeneic bone marrow transplantation (BMT) or stem cell transplantation (SCT) has also been applied with curative intent. Added that long-term data beyond 10 years of therapy are available, and most long-term survivors show no evidence of the BCR/ABL translocation by any available test; however, some patients are not eligible for this approach because of age, comorbid conditions, or lack of a suitable donor. In addition, substantial morbidity and mortality result from allogeneic BMT or SCT; a 5% to 10% treatment-related mortality can be expected, depending on whether a donor is related and on the presence of mismatched antigens. Also added that in a prospective trial of 427 transplant-eligible, previously untreated patients, 166 patients were allocated to allogeneic SCT, and 261 patients were allocated to drug treatment; there was no difference in 10-year OS (cited Gratwohl et al. as reference 11 and level of evidence 3iiiA).
Added text to state that imatinib mesylate and the newer tyrosine kinase inhibitors, along with allogeneic SCT, have contributed to a life expectancy for a newly diagnosed patient in 2013 that is only 3 life-years fewer than that of the general population (cited Bower et al. as reference 15).
Added text to state that at 5 years, there was no difference in PFS or OS. Revised text about the progression to accelerated-phase CML or blast crisis that occurred in 13 patients on imatinib and in 6 patients on dasatinib (cited Cortes et al. as reference 9).
Revised text to state that although one of these two studies showed statistically significant decreased rates of progression to accelerated- or blastic-phase CML, the 5- to 10-year follow-up period with nilotinib and dasatinib demonstrated a survival for these agents similar to that for imatinib.
Added text to state that a single-arm clinical trial using first-line imatinib with either selective imatinib intensification or selective switching to nilotinib resulted in a 3-year OS of 96% and transformation-free survival of 95%, with a confirmed major molecular response rate of 73% at 24 months (cited Yeung et al. as reference 27 and level of evidence 3iiiDiv). Also added that all patients started treatment with imatinib and were given 600 mg daily. Imatinib plasma trough levels that were under 1,000 ng/mL on day 22 prompted an increase of imatinib to 800 mg daily. Molecular targets were set, and failure to reach these targets prompted an increase of imatinib to 800 mg daily or a switch to nilotinib. The molecular target rates for BCR-ABL at 3, 6, or 12 months were given.
Added text to state that this strategy of employing front-line imatinib is an alternative to the immediate use of more-potent tyrosine kinase inhibitors, such as nilotinib and dasatinib.
Added text to answer the question of whether the newer tyrosine kinase inhibitors, dasatinib and nilotinib, should replace imatinib as front-line therapy by stating that randomized trials have failed to confirm OS differences. Also added that imatinib blood levels and timed molecular targets that informed of the need for increased doses of imatinib may make any clinical differences between nilotinib, dasatinib, and imatinib more about side effects than about efficacy.
Added text that reviewed several retrospective reports to answer the question of whether patients who obtain a complete molecular remission can discontinue therapy with tyrosine kinase inhibitors; provided three summarizations of the data (cited Hughes et al. as reference 30 and level of evidence 3iiiDiv).
Added text to state that the duration of remissions after a successful reinduction with a previous tyrosine kinase inhibitor or the depth of subsequent responses with reinduction of a previous tyrosine kinase inhibitor is not known; at this time, there are insufficient data to recommend routinely stopping tyrosine kinase inhibitors, even in this select group of patients.
ver historia personal en: www.cerasale.com.ar [dado de baja por la Cancillería Argentina por temas políticos, propio de la censura que rige en nuestro medio]//
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weblog.maimonides.edu/farmacia/archives/0216_Admin_FarmEcon.pdf - //
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