Comprehensive therapeutic outcomes of frontline imatinib mesylate in newly diagnosed chronic phase chronic myeloid leukemia patients in Korea: feasibility assessment of current ELN recommendation
ABSTRACT Optimal responses during imatinib therapy are commonly defined following the European LeukemiaNet (ELN) recommendations. Achievements of these optimal responses have not, however, been comprehensively tested as response-related prognostic factors using single center data sets. We evaluated the parameters using long-term (median 63 months) outcomes from 363 chronic phase chronic myeloid leukemia patients treated with imatinib as frontline therapy at our center. Intention-to-treat analysis showed comparable rates of complete cytogenetic response (86 %), major molecular response (MMR, 54 %), and complete molecular response (MR(4.5), 8 %). Estimated overall survival, progression-free survival, and event-free survival at 7 years were 94, 88 and 84 %, respectively. Achievement of recommended optimal response at 6 months (major cytogenetic response) and 12 months (complete cytogenetic response) yielded significantly better overall, progression-free, and event-free survival. However, achievement of recommended optimal response at 18 months (MMR) provided marginal benefit only in event-free survival. Most ELN criteria were predictive of long-term outcomes, with the exception of the clinical significance of achieving MMR at 18 months. Treatment adherence in the early treatment period was one of the important independent predictors of favorable long-term outcome. Durable cytogenetic and molecular responses were maintained in a majority of patients treated with optimal dose intensity.
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ABSTRACT: Clinical evidence in chronic myeloid leukemia demonstrates a significant link between optimal response to tyrosine kinase inhibitor (TKI) therapy and favorable clinical outcome. For patients with suboptimal response to first-line TKI, clinical data show that a considerable proportion can be rescued by second-line TKI. Practice guidelines now recommend that clinicians consider a switch in TKI for patients with suboptimal response as early as 3 months after first-line TKI initiation, thus allowing clinicians to intervene in a timely manner and consider the potential benefit of a switch in TKI therapy.Leukemia research 02/2013; 37(5). DOI:10.1016/j.leukres.2013.01.006 · 2.35 Impact Factor
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ABSTRACT: Although recent studies have suggested that cessation of imatinib (IM) in chronic myeloid leukemia patients can be associated with sustained response, further validation is needed to explore predictive factors. In a prospective, multicenter study, chronic phase patients were eligible for cessation of IM therapy after more than 3 years if they had no detectable BCR-ABL1 transcript for at least 2 years. A total of 48 patients with a median age of 47 years (19-74 years) were enrolled. Twenty patients received IM for post-transplant relapse. After a median follow-up of 15.8 months (1.4-28.2 months) after IM discontinuation, nine of the non-transplant group lost undetectable molecular residual disease (UMRD) and major molecular response (MMR), whereas none of the 20 patients in the transplant group experienced UMRD loss. Probabilities for sustained MMR and UMRD were 64.4% and 66.3% in the non-transplant group, respectively. Of nine patients re-treated with IM, eight patients re-achieved MMR at a median of 1.7 months (0.9-2.8 months). Seven of these patients re-achieved UMRD at a median of 5.6 months (2.8-12.1 months). Previous transplantation, IM duration, and UMRD duration were significantly associated with sustained molecular responses. Our data strongly suggest that immunological control contributes to sustained suppression of residual leukemia cell expansion and that IM can be safely discontinued in patients with post-transplant relapse. Am. J. Hematol., 2013. © 2013 Wiley Periodicals, Inc.American Journal of Hematology 06/2013; 88(6). DOI:10.1002/ajh.23427 · 3.80 Impact Factor
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ABSTRACT: Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors (TKIs), mandate regular updating of concepts and management. An ELN expert panel reviewed prior and new studies, to update recommendations made in 2009. We recommend as initial treatment imatinib or nilotinib or dasatinib. Response is assessed with standardized RQ-PCR and/or cytogenetics at 3, 6, and 12 months. BCR-ABL1 transcript levels ≤10% at 3 months, <1% at 6 months, and ≤0.1% from 12 months onward, define optimal response, while >10% at 6 months and >1% from 12 months onward define failure, mandating a change of treatment. Similarly, partial cytogenetic response (PCyR) at 3 months and complete CyR (CCyR) from 6 months onward define optimal response, while no CyR (Ph+>95%) at 3 months, less than PCyR at 6 months, and less than CCyR from 12 months onward, define failure. Between optimal and failure, there is an intermediate warning zone requiring more frequent monitoring. Similar definitions are provided for response to 2nd line therapy. Specific recommendations are made for patients in accelerated and blastic phase, and for allogeneic stem cell transplantation. Optimal responders should continue therapy indefinitely, with careful surveillance, or can be enrolled in controlled studies of treatment discontinuation, once a deeper molecular response is achieved.Blood 06/2013; 122(6). DOI:10.1182/blood-2013-05-501569 · 10.45 Impact Factor