The argument for using imatinib in CML

Abstract

June 2018 was the 20th anniversary of the clinical use of the first tyrosine kinase inhibitor (TKI), imatinib, for chronic myeloid leukemia. Since then, the change in prognosis for patients with this disease is one of the major success stories of modern cancer medicine. The dilemmas that face physicians and patients are no longer only those concerned with delaying inevitable progression to the terminal blastic phase or selecting the individuals most likely to benefit from allogeneic stem-cell transplantation; rather, they are now focused also on the choice of TKI, the management of comorbidities and adverse effects, strategies to improve quality of life, and the appropriateness of a trial of therapy discontinuation. Interestingly, with 4 TKIs approved for frontline use, the choice of initial therapy continues to cause controversy, a situation made more complicated by the tantalizing prospect of treatment-free remission. In this manuscript, we will explore the factors influencing this decision and try to provide a pragmatic and clinically applicable solution.

The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in chronic myeloid leukemia

“…Despite significantly faster achievement of molecular reponses with second generation TKIs [10,13,[30][31][32][33], first-line treatment with imatinib and its generics is still widespread. Most physicians continue to see room for first-line treatment with imatinib depending on age, comorbidities, kinase domain mutations, treatment goal, costs, and availability of generic imatinib [1,[33][34][35][36][37]. In prognostic support of first-line treatment selection, the ELTS score offers the most appropriate risk group classification.…”

“…In prognostic support of first-line treatment selection, the ELTS score offers the most appropriate risk group classification. This is also of interest as imatinib has fewer side effects than second generation TKIs, and it is perceived that a statistically significant overall superiority in long-term efficacy over imatinib has not yet been shown for another TKI [1,33,36,37]. There is indication that the ELTS score would also discriminate risk groups with respect to long-term survival if a second generation TKI were chosen as first-line treatment [24].…”

BCR‐ABL tyrosine kinase inhibitors promote pathological changes in dilator phenotype in the human microvasculature

“…As standard clinical practice recommends continuous treatment of patients with CML with BCR‐ABL TKIs, future studies of vascular function in this patient population are warranted. It is interesting to note that of all clinically used BCR‐ABL TKIs, imatinib has the fewest reported adverse events, including those of cardiovascular nature 3,21 . Our data, however, show that imatinib and nilotinib have similar negative impacts on human microvascular function, which is concerning as nilotinib has been reported to have serious off‐target effects 22 .…”

Philadelphia Chromosome-Positive Leukemia in the Lymphoid Lineage—Similarities and Differences with the Myeloid Lineage and Specific Vulnerabilities

“…The multicenter study recently published by Efficace et al demonstrated better health-related quality of life in patients treated with dasatinib than imatinib in frontline therapy [ 95 ]. The treatment response and survival outcomes of CML patients to the 1st line TKIs are summarized in [ 96 ]. A recent noteworthy fact is that approximately 40–50% CML patients with deep and durable molecular responses can safely discontinue therapy [ 91 , 97 , 98 ].…”