Imatinib as the first‐line treatment of patients with chronic myeloid leukemia diagnosed in the chronic phase: Can we compare real life data to the results from clinical trials?

Žáčková, Daniela; Klamová, Hana; Dušek, Ladislav; Mužı́k, Jan; Poláková, Kateřina Machová; Moravcová, Jana; Jurček, Tomáš; Dvořáková, Dana; Ráčil, Zdeněk; Pospíšil, Zdeněk; Oltová, Alexandra; Michalova, Kyra; Březinová, Jana; Rázga, Filip; Doubek, Michael; Cetkovský, Petr; Trněný, Marek; Mayer, Jiřı́

doi:10.1002/ajh.21942

Cited by 16 publications

(19 citation statements)

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“…Zackova et al studied 152 CML-CP patients treated frontline with imatinib, and reported 4 year cumulative incidence of CHR and CCyR as 95.3% and 80.6%, respectively. The 4 year OS and PFS was 91.5% and 78.1%, respectively 13 . De Lavallade et al also reported similar excellent outcomes of CML patients treated outside of a clinical trial (5 year cumulative CHR: 98.5%, CCyR: 82.7%, 5 year OS: 83.2%, PFS: 82.7%) 11 .These results suggests similar outcomes as observed in IRIS trial or clinical trial in our institution 6,14 .…”

Section: Discussionmentioning

confidence: 98%

“…Authors compared their results with several imatinib clinical trials, including IRIS 10 (CCyR were 69% and 76% at 12 and 18 months, respectively), and it was concluded that imatinib may have lower efficacy in CML patients treated in community hospitals comparing to the results reported in clinical trials 7 . Other studies have reported outcomes of CML patients treated outside of a clinical trial 11–13 . Zackova et al studied 152 CML-CP patients treated frontline with imatinib, and reported 4 year cumulative incidence of CHR and CCyR as 95.3% and 80.6%, respectively.…”

Section: Discussionmentioning

confidence: 99%

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Similar Outcome of Patients With Chronic Myeloid Leukemia Treated With Imatinib in or Out of Clinical Trials

Yılmaz

Kantarjian

Jabbour

et al. 2013

Clinical Lymphoma Myeloma and Leukemia

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Introduction Outcomes of CML-CP patients treated in clinical trials are frequently perceived to not be representative of those treated outside of clinical trials. Materials and Methods We investigated the outcomes of patients receiving imatinib outside of a clinical trial (off protocol) or on a clinical trial (on protocol) for CML-CP. Results We identified 65 patients treated with imatinib off protocol and 71 patients treated on protocol with standard-dose imatinib. The overall complete cytogenetic response (CCyR) rates were 83% and 83% for patients treated on and off protocol, respectively. CCyR rates 12 months after initiation of imatinib were not different (61% vs 66%, respectively; p=.15). Patients treated off protocol had similar rates of overall major molecular response (72% vs 73%) compared to the patients treated on protocol. The 5-year event free survival rates were 84% and 86% for off and on protocol patients, respectively. There was also no significant difference in 5-year transformation free survival (94% vs 96%) and overall survival (96% vs 90%). Conclusion These results suggest that patients with CML treated outside of a clinical trial may have the same excellent outcome as those treated on a clinical trial provided they are followed with the same rigor.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Similar Outcome of Patients With Chronic Myeloid Leukemia Treated With Imatinib in or Out of Clinical Trials

Yılmaz

Kantarjian

Jabbour

et al. 2013

Clinical Lymphoma Myeloma and Leukemia

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“…For CML, as with many other cancers, discrepancies between trial and population-based studies are commonly ascribed to systematic differences between the types of patients recruited into trials and those who are not; the former often tending to be comprised of younger patients with fewer comorbidities and less advanced disease 7 9 15. In addition, it is becoming ever more apparent that non-trial access to expensive drugs such as TKIs has a key role to play in countries without universal healthcare coverage 1 16–18.…”

Section: Introductionmentioning

confidence: 99%

Determinants of survival in patients with chronic myeloid leukaemia treated in the new era of oral therapy: findings from a UK population-based patient cohort

et al. 2014

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ObjectivesTo examine contemporary survival patterns in the general population of patients diagnosed with chronic myeloid leukaemia (CML), and to identify patient groups with less than optimal outcomes.DesignProspective population-based cohort.SettingThe UK's Haematological Malignancy Research Network (catchment population 3.6 million, with >2000 new haematological malignancies diagnosed annually).ParticipantsAll patients newly diagnosed with CML, from September 2004 to August 2011 and followed up to 31 March 2013.Main outcome measureIncidence and survival.ResultsWith a median diagnostic age of 59 years, the CML age standardised (European) incidence was 0.9/100 000 (95% CIs 0.8 to 0.9), 5-year overall survival was 78.9% (72.3 to 84.0) and 5-year relative survival 88.6% (81.0 to 93.3). The efficacy of treatment across all ages was clearly demonstrated; the relative survival curves for those under 60 and over 60 years being closely aligned. Survival findings were similar for men and women, but varied with deprivation; the age and sex adjusted HR being 3.43 (1.89 to 6.22) for deprivation categories 4–5 (less affluent) versus 1–3 (more affluent). None of these differences were attributable to the biological features of the disease.ConclusionsWhen therapy is freely provided, population-based survival for CML is similar to that reported in clinical trials, and age loses its prognostic significance. However, although most of the patients with CML now experience close to normal lifespans, those living in more deprived areas tend to have poorer outcomes, despite receiving the same clinical care. A significant improvement in overall population outcomes could be achieved if these socioeconomic differences, which may reflect the treatment compliance, could be eliminated.

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“…In such a situation, the panel considers that the ATFS method, as documented by Zackova et al, 38 is a reasonable approach to assess the usefulness of a study treatment. Some reasons for switching to an alternative treatment may be subjective in some patients, but the switch per se is a robust marker; the study treatment is replaced, and the date of switch is easily assessable.…”

Section: Analyses Of Responses Over a Period Of Timementioning

confidence: 99%

Definitions, methodological and statistical issues for phase 3 clinical trials in chronic myeloid leukemia: a proposal by the European LeukemiaNet

Guilhot

Baccarani

Clark

et al. 2012

Blood

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The treatment policy of chronic myeloid leukemia (CML), particularly with tyrosine kinase inhibitors, has been influenced by several recent studies that were well designed and rapidly performed, but their interpretation is of some concern because different end points and methodologies were used. To understand and compare the results of the previous and future studies and to translate their conclusion into clinical practice, there is a need for common definitions and methods for analyses of CML studies. A panel of experts was appointed by the European LeukemiaNet with the aim of developing a set of definitions and recommendations to be used in design, analyses, and reporting of phase 3 clinical trials in this disease. IntroductionApplied statistics are important tools in medical evaluations. The relevance of statistical designs and statistical results in trials is based on concise definitions regarding diagnosis, management, and treatment strategies. The choice of adequate statistical tests depends on the parameters to be analyzed and on specific end points.After the initial descriptions of chronic myeloid leukemia (CML) more than 160 years ago, little progress was made in its treatment for more than a century. 1 Survival prolongation was first achieved with drugs, such as hydroxyurea. 1 Then, major improvements were obtained with allogeneic hematopoietic stem cell transplantation. First priority at that time was to analyze survival.The understanding of the pathogenesis of CML began with the discovery of the Philadelphia (Ph) chromosome followed later on by the recognition of its molecular counterpart, the BCR-ABL fusion gene. In CML, clinical trials performed during the past 2 to 3 decades have profoundly improved the outcome of patients with CML. 2 In Europe, the coordinators of national CML Study Groups (European Investigators on CML) joined forces to perform European trials and long-term observations, 3 to conduct common meta-analyses, 4,5 and to elaborate new prognostic scores. 6,7 With the advents of IFN-␣ and of tyrosine kinase inhibitors (TKIs), analyses of treatment response moved more into focus.Thus, the relationship between responses and survival became of particular interest. The cytogenetic outcome is usually considered as a reliable surrogate marker for survival in CML, 7,8 whereas the relationship between molecular response and survival is still under investigation. 9 Molecular response is probably more relevant to the issue of treatment discontinuation without relapse and cure. 10 On the other hand, because of the recent improvement of survival offered by the use of TKIs, other diseases and deaths from causes other than CML progression have become more frequent in CML patients. Analysis of survival may include these new parameters. Quality of life and compliance have also to be considered in the context of this chronic disease with an expected long duration of treatment.Consequently, statistical methods in addition to Kaplan-Meier (KM) 11 analyses and initial Cox regression models 12 should be a...

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Imatinib as the first‐line treatment of patients with chronic myeloid leukemia diagnosed in the chronic phase: Can we compare real life data to the results from clinical trials?

Cited by 16 publications

References 16 publications

Similar Outcome of Patients With Chronic Myeloid Leukemia Treated With Imatinib in or Out of Clinical Trials

Similar Outcome of Patients With Chronic Myeloid Leukemia Treated With Imatinib in or Out of Clinical Trials

Determinants of survival in patients with chronic myeloid leukaemia treated in the new era of oral therapy: findings from a UK population-based patient cohort

Definitions, methodological and statistical issues for phase 3 clinical trials in chronic myeloid leukemia: a proposal by the European LeukemiaNet

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