Abstract
BackgroundThe current situation in the treatment of chronic myeloid leukaemia (CML) presents a new challenge for attempts to measure the therapeutic results, as the CML patients can experience multiple leukaemia-free periods during the course of their treatment. Traditional measures of treatment efficacy such as leukaemia-free survival and cumulative incidence are unable to cope with multiple events in time, e.g. disease remissions or progressions, and as such are inappropriate for the efficacy assessment of the recent CML treatment.MethodsStandard nonparametric statistical methods are used for estimating two principal characteristics of the current CML treatment: the probability of being alive and leukaemia-free in time after CML therapy initiation, denoted as the current cumulative incidence of leukaemia-free patients; and the probability that a patient is alive and in any leukaemia-free period in time after achieving the first leukaemia-free period on the CML treatment, denoted as the current leukaemia-free survival. The validity of the proposed methods is further documented in the data of the Czech CML patients consecutively recorded between July 2003 and July 2009 as well as in simulated data.ResultsThe results have shown a difference between the estimates of the current cumulative incidence function and the common cumulative incidence of leukaemia-free patients, as well as between the estimates of the current leukaemia-free survival and the common leukaemia-free survival. Regarding the currently available follow-up period, both differences have reached the maximum (12.8% and 20.8%, respectively) at 3 years after the start of follow-up, i.e. after the CML therapy initiation in the former case and after the first achievement of the disease remission in the latter.ConclusionsTwo quantities for the evaluation of the efficacy of current CML therapy that may be estimated with standard nonparametric methods have been proposed in this paper. Both quantities reliably illustrate a patient's disease status in time because they account for the proportion of patients in the second and subsequent disease remissions. Moreover, the model is also applicable in the future, regardless of what the progress in the CML treatment will be and how many treatment options will be available, respectively.
Highlights
The current situation in the treatment of chronic myeloid leukaemia (CML) presents a new challenge for attempts to measure the therapeutic results, as the CML patients can experience multiple leukaemia-free periods during the course of their treatment
To demonstrate the usability of the proposed statistical estimates, we applied them to representative records on all consecutive chronic phase CML (CP-CML) patients treated by first-line imatinib in two Czech haematological centres in Prague and Brno [18]
152 consecutively recorded CPCML patients received the first-line imatinib between July 2003 and July 2009; all records were registered in the Czech database called INFINITY
Summary
The current situation in the treatment of chronic myeloid leukaemia (CML) presents a new challenge for attempts to measure the therapeutic results, as the CML patients can experience multiple leukaemia-free periods during the course of their treatment. Treatment guidelines and recommendations for patients treated for chronic myeloid leukaemia (CML) have changed dramatically over the last decade, as a BCRABL tyrosine kinase inhibitor (TKI), imatinib, was introduced in 1998 [1,2]. Even in the era of imatinib, CML remains a chronic disease, requiring lifelong therapy with various consecutive strategies. Second-generation TKIs should be mentioned due to their potential to achieve or return and maintain cytogenetic response in approximately 50% of resistant/ intolerant CP-CML patients already treated by imatinib [5,6,7]. Current medicine offers powerful tools with the potential to improve reachable therapeutic outcomes
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