Chronic myeloid leukemia: 2016 update on diagnosis, therapy, and monitoring

Abstract

Disease overview: Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1‐2 cases per 100,000 adults. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults. Diagnosis: CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR‐ABL1 fusion oncogene, which in turn translates into a BCR‐ABL oncoprotein. Frontline therapy: Three tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib are approved by the United States Food and Drug Administration for first‐line treatment of patients with newly diagnosed CML in chronic phase (CML‐CP). Clinical trials with 2nd generation TKIs reported significantly deeper and faster responses; their impact on long‐term survival remains to be determined. Salvage therapy: For patients who fail frontline therapy, second‐line options include second and third generation TKIs. Although second and third generation TKIs are potent and selective TKIs, they exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients’ comorbidities, disease stage, and BCR‐ABL1 mutational status. Patients who develop the T315I “gatekeeper” mutation display resistance to all currently available TKIs except ponatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML‐CP who have failed at least two TKIs, and for all patients in advanced phase disease. Am. J. Hematol. 91:253–265, 2016. © 2015 Wiley Periodicals, Inc.

The value of quality of life assessment in chronic myeloid leukemia patients receiving tyrosine kinase inhibitors

“…With 3 TKIs that can be used for frontline treatment (ie, imatinib, dasatinib, and nilotinib), and the same drugs plus bosutinib that can be used as second-line or greater therapy, 32 treatment decisions in daily practice are often challenging. For example, appropriate management of intolerance and AEs is crucial in clinical practice, and several strategies can be used to help patients reduce symptom burden 33 and improve QoL, including timely switching to another TKI.…”

Budget Impact analysis of the first-line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) adult patients

“…Currently, guidelines recommend three drugs for the initial management of a newly diagnosed CML-CP patient: imatinib, dasatinib, and nilotinib. Imatinib was the first TKI class drug approved by the US Food and Drug Administration for the treatment of CML-CP [3]. In the following years, second-generation TKIs -dasatinib and nilotinib -were introduced, all showing the ability to induce molecular and cytogenetic responses in patients who had failed therapy with imatinib.…”

“…In order to calculate the estimated costs of CML patients on first-line treatment with TKI drugs, an Excel-based Budget Impact model, able to simulate the therapeutic pathway of the patients undergoing treatment with the of 3-5 years; the accelerated phase (AP), a short, intermediate phase characterized by a different clinical symptomatology; and the blast phase (BP) -or crisis -, a stage where the disease is acute and terminal [3,4]. At the time of diagnosis, approximately 85% of patients are in the chronic phase, while in the remaining 15% a more advanced disease phase is already evident [4].…”

“…patients with newly diagnosed, not-yet-advanced CML-CP. In particular, to the population resident in Italy in 2016 [14], the rate of incidence of the disease was applied (1-2 cases per 100,000 [3]). The model assumes that, out of the 912 diagnosed patients, 15% are not eligible for treatment, since they have been identified in an already advanced stage of the disease [4].…”

Chronic Myeloid Leukemia in a Patient With Multiple Sclerosis Treated With Interferon Beta-1a

“…The diagnosis of CML is based on characteristic histopathological findings and presence of the Philadelphia (Ph1) chromosome in the peripheral blood and bone marrow cells [1]. Interferon (IFN) beta-1a is approved for the treatment of patients with relapsing forms of multiple sclerosis (MS) [2].…”