Kendra Sweet

Quality of life outcomes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a controlled comparison

PurposeTyrosine kinase inhibitors (TKIs) are now standard treatment for chronic myeloid leukemia (CML). While TKIs have less toxicity than previous treatments, they have side effects that can impact quality of life (QOL).MethodsThis study compared CML patients taking a TKI for an average of 4.01xa0years (range 0.50–9.79xa0years) to age- and gender-matched controls with no history of cancer on measures of symptom burden, depression, fatigue, sleep, and health-related QOL.ResultsCompared to controls (nu2009=u200962), CML patients (nu2009=u200962) taking a TKI (imatinib 55xa0%, nilotinib 31xa0%, and dasatinib 14xa0%) reported significantly worse fatigue severity (pu2009<u2009.001), fatigue interference (pu2009<u2009.001), depression (pu2009=u2009.007), symptom burden (pu2009<u2009.001), and physical QOL (pu2009<u2009.001). TKI patients were also more likely meet established cutoffs for clinically meaningful fatigue (p valuesu2009<u2009.001) and depression (pu2009=u2009.004). There were no differences in mental QOL or sleep (p valuesu2009>u2009.010). Regarding specific symptoms, TKI patients were more likely to report nausea, diarrhea, itching, skin changes, swelling of arms or legs, and not looking like themselves (p valuesu2009<u2009.001).ConclusionsThese data suggest the need for interventions to address QOL in CML patients taking TKIs.

Biomarkers for determining the prognosis in chronic myelogenous leukemia.

The introduction of BCR-ABL1 tyrosine kinase inhibitors (TKIs) for treatment of chronic myelogenous leukemia in chronic phase (CML-CP) has revolutionized therapy, altering the outcome from one of shortened life expectancy to long-term survival. With over 10xa0years of long-term treatment with imatinib and several years of experience with the next generation of TKIs, including nilotinib, dasatinib, bosutinib, and ponatinib, it is becoming clear that many clinical parameters have great impact on the prognosis of patients with CML. Emerging novel gene expression profiling and molecular techniques also provide new insights into CML pathogenesis and have identified potential prognostic markers and therapeutic targets. This review presents the supporting data and discusses how certain clinical characteristics at diagnosis, the depth of early response, the presence of certain kinase domain mutations, and additional molecular changes serve as prognostic factors that may guide individualized treatment decisions for patients with CML-CP.

Novel Therapeutics in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a heterogenous disease, and the standard treatment with cytotoxic chemotherapy has remained largely unchanged for over four decades. As more is being learned about AML and the potential molecular targets found within the leukemia cells, an abundance of targeted therapies are becoming available for study in the treatment of this challenging disease. This review serves to provide a brief overview of some of several agents currently being studied and developed in AML.

The one-two punch: combination treatment in chronic myeloid leukemia.

Despite the success of tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia (CML), minimal residual disease persists, requiring indefinite treatment. Accumulated evidence has shown that leukemic stem cells (LSCs) in the bone marrow can survive TKI treatment via downstream BCR-ABL1-independent signaling pathways that are activated by soluble growth factors and interactions with the extracellular matrix in the bone marrow microenvironment. Research efforts have therefore turned to the identification and development of agents that target LSCs, and together with TKIs, have the potential to eradicate CML. A number of such agents are now under clinical investigation, and others are soon to enter early-phase studies. This review examines the pathways, molecular targets, and potential new therapeutics that, with TKIs, may provide an effective one-two punch to cure CML.

Early switch in tyrosine kinase inhibitor therapy for patients with chronic myeloid leukemia: An emerging clinical question.

Response to frontline BCR-ABL1-targeted tyrosine kinase inhibitor (TKI) therapy is associated with an improved prognosis for patients with chronic myeloid leukemia (CML). Accordingly, the National Comprehensive Cancer Network (NCCN) and European LeukemiaNet (ELN) recommend the use of specific response milestones (eg, BCR-ABL1≤10% on the International Scale at 3 months) to assess treatment success and inform follow-up care, including potentially switching to another TKI therapy. However, prior to any treatment change, the potential benefits and risks of each TKI and the goals of the patient must be considered. Here we review current NCCN and ELN response recommendations for patients with CML, highlight the impact of early responses on long-term prognosis, and discuss several reasons patients may consider a switch in TKI therapy. We also review completed and ongoing clinical studies involving a switch in frontline therapy for patients with CML, including those with a treatment-free remission phase.

Clinical advances in the management of chronic myelogenous leukemia: focus on bosutinib and patient considerations.

The treatment for chronic myeloid leukemia has changed significantly over the past 15 years, and as of now, there are five BCR-ABL1 (breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1) tyrosine kinase inhibitors that have gained approval for treatment of this disease. All five are very effective drugs, and the decision surrounding which to use in specific patients is based on numerous factors. Bosutinib is one of the newer tyrosine kinase inhibitors to gain approval, and has been studied in the first-line setting as well as after failure of other tyrosine kinase inhibitors. It is an SRC-ABL1 (steroid receptor co-activator-ABL1) inhibitor that works in the presence of most kinase domain mutations. The primary side effects of bosutinib are gastrointestinal upsets. In the appropriate clinical setting, bosutinib can be considered a valuable addition to the armamentarium of treatments available for chronic myeloid leukemia.

NCCN and ELN: What do the guidelines tell us?

The prognosis for patients with Chronic Myeloid Leukemia is vastly different in 2016 compared to 20 years ago, and this is due to the development of BCR-ABL tyrosine kinase inhibitors (TKIs). As newer, more potent, TKIs have been developed and approved over the past 15 years, the decision about which drug to use as first line therapy, and when to switch treatment in particular patients has become more complicated. The National Comprehensive Cancer Network (NCCN) and the European LeukemiaNet (ELN) have developed treatment and monitoring guidelines to aide in the management of these patients. The guidelines were developed by two groups of CML experts and recommendations are based on available data and expert opinion. With adherence to the recommendations proposed by the NCCN and ELN, we can expect to continue to see excellent outcomes for our patients with CML.