1,720,995 research outputs found
Future Management of Chronic Myeloid Leukemia: From Dose Optimization to New Agents
No full textBackground: The outcome of chronic myeloid leukemia (CML) patients in chronic phase has changed after the introduction of tyrosine kinase inhibitors (TKIs). The life expectancy is actually similar to that of the general population. Although outstanding results were achieved, about 20-30% of patients failed to achieve molecular milestones or experienced a severe toxicity and needed to switch to a second line. Objective: The aim of this review is to report on possible future management in CML, from dose optimization to avoid long-term off-target events to new agents for the treatment of resistant and/or intolerant patients. Methods: Broad research on Medline, Embase and archives from EHA and ASH congresses was performed. Results: New TKIs have been developed to counteract resistance and/or intolerance in the setting of T315I mutated patients. The benefits of ponatinib dose optimization have been recently reported in the OPTIC trial. New trials to test the dose optimization are ongoing. Conclusion: Reduction of the standard dose could be performed to reduce the specific TKI toxicity. Selective TKIs could be prescribed in the future as third line treatment
Asciminib: an investigational agent for the treatment of chronic myeloid leukemia
No full textIntroduction: Tyrosine kinase inhibitors (TKIs) have drastically changed the outcome of chronic myeloid leukemia (CML) patients. However, a subset of patients experienced resistance and/or intolerance and need to switch to other agents. Resistance to second-generation TKIs used in first-line treatment is less of an issue when compared to imatinib in first line. New drugs that are able to improve efficacy, without long-term off-target effects are needed. Allosteric inhibitors such as asciminib (ABL001) were created to overcome resistance and off-target toxicity. Areas covered: In this review, we report the mechanism of action, pharmacokinetic data, and the clinical trial results of asciminib tested in chronic phase CML patients. Expert Opinion: Asciminib, the first example of allosteric inhibition, could be a promising approach as third-line therapy and in the subset of patients with T315I mutation that, for coexistent comorbidities, cannot receive other drugs. Future results will probably help to move the drug to earlier lines of treatment
Insights into the optimal use of ponatinib in patients with chronic phase chronic myeloid leukaemia
No full textThere are five tyrosine kinase inhibitors (TKIs) that are currently approved (in the European Union and the United States) for the treatment of chronic myeloid leukaemia (CML) in the chronic phase (CP) and each of them has its own efficacy and toxicity profile. Oral ponatinib (Iclusig((R))) is a third-generation TKI structurally designed to inhibit native BCR-ABL1 tyrosine kinase and several BCR-ABL1 mutants, including T315I. Ponatinib is now approved for patients with CML who are resistant or intolerant to prior TKI therapy (European Union) or for whom no other TKI therapy is indicated (United States). Despite achieving results in heavily treated patients, which led to its approval, the drug may induce cardiovascular events, requiring a careful baseline assessment of predisposing risk factors and specific management during treatment. Pharmacokinetic analysis has indicated the possibility of reducing the starting dose of ponatinib to 15 mg/day and preliminary data showed advantages in terms of safety while maintained its efficacy. This review summarizes the results achieved and drug-related side effects reported in all clinical trials and real-life experiences, testing ponatinib in patients with CP-CML. In addition, we focus on the appropriate use of ponatinib in clinical practice suggesting some useful recommendations on the proper management of this drug
Improvement of bone marrow fibrosis with ruxolitinib: Will this finding change our perception of the drug?
No full textRuxolitinib, a JAK1 and JAK2 inhibitor, has been tested and approved for the treatment of primary and secondary myelofibrosis. Reduction of spleen volume and improvement of constitutional symptoms and quality of life have been reported as the major findings in sponsored randomized clinical trials. Recent data indicated that the drug improves bone marrow fibrosis and that different targets may be involved in this response. These new data, which require confirmation in prospective trials, may change our perspectives and therapeutic strategies for this disease.Ruxolitinib, a JAK1 and JAK2 inhibitor, has been tested and approved for the treatment of primary and secondary myelofibrosis. Reduction of spleen volume and improvement of constitutional symptoms and quality of life have been reported as the major findings in sponsored randomized clinical trials. Recent data indicated that the drug improves bone marrow fibrosis and that different targets may be involved in this response. These new data, which require confirmation in prospective trials, may change our perspectives and therapeutic strategies for this disease
Insights into the optimal use of ponatinib in patients with chronic phase chronic myeloid leukaemia
No full textThere are five tyrosine kinase inhibitors (TKIs) that are currently
approved (in the European Union and the United States) for the treatment
of chronic myeloid leukaemia (CML) in the chronic phase (CP) and each of
them has its own efficacy and toxicity profile. Oral ponatinib
(Iclusig((R))) is a third-generation TKI structurally designed to
inhibit native BCR-ABL1 tyrosine kinase and several BCR-ABL1 mutants,
including T315I. Ponatinib is now approved for patients with CML who are
resistant or intolerant to prior TKI therapy (European Union) or for
whom no other TKI therapy is indicated (United States). Despite
achieving results in heavily treated patients, which led to its
approval, the drug may induce cardiovascular events, requiring a careful
baseline assessment of predisposing risk factors and specific management
during treatment. Pharmacokinetic analysis has indicated the possibility
of reducing the starting dose of ponatinib to 15 mg/day and preliminary
data showed advantages in terms of safety while maintained its efficacy.
This review summarizes the results achieved and drug-related side
effects reported in all clinical trials and real-life experiences,
testing ponatinib in patients with CP-CML. In addition, we focus on the
appropriate use of ponatinib in clinical practice suggesting some useful
recommendations on the proper management of this drug
Correlation between Charlson comorbidity index and outcome in patients with chronic phase chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors upfront
No full textMeasuring prognosis in chronic myeloid leukemia: what's new?
No full textIntroduction: The outcome of chronic myeloid leukemia (CML) patients in chronic phase has changed after the introduction of tyrosine kinase inhibitors (TKIs). The life expectancy is actually similar to that of the general population. Prognostic stratification at baseline is part of a patient-centered approach to decide the best therapeutic approach. Areas covered: In this review, the current prognostic factors examined at baseline are detailed and the meaning is explained. A broad research on Medline, Embase and archives from EHA and ASH congresses, was performed. Prognostic factors have been divided into patient-related (age, gender, comorbidities, etc.) and disease-related (additional cytogenetic abnormalities, type of transcript, etc). New information about genomic data and the potential role of patient-reported outcomes is also discussed. Expert Opinion: Prognostic factors at baseline should be considered to evaluate the long-term probability of disease-related death, the possible toxicity, and the projected long-term overall survival. The genomic assessment would provide the basis for a genomic-based risk and help in oriented decision-making process
Tyrosine kinase inhibitor discontinuation in the management of chronic myeloid leukemia: a critical review of the current practice
No full textIntroduction: Tyrosine kinase inhibitors (TKIs), which target BCR-ABL1 kinase activity, have significantly prolonged the overall survival of patients affected by chronic myeloid leukemia (CML) and changed drastically the outcome. Evidences from several studies suggest that in patients who have achieved a sustained, stable and deep molecular response, TKI treatment can be safely discontinued with a close subsequent monitoring. Thus, a stable deep molecular response (DMR) has become a feasible treatment goal in CML. Areas covered: In this review, the main findings extrapolated from sponsored and real-life evidences regarding TKI discontinuation were discussed, through a broad research on Medline, Embase and archives from EHA and ASH congresses (including words such as discontinuation, treatment-free remission, TFR, etc). Moreover, suggestions emerged from international guidelines about treatment-free remission (TFR) are presented. Expert opinion: With the growing availability of clinical trials and real-life data on TFR, in recent years the possibility of offering to CML patients a safe, informed and shorter path to TFR, through the achievement of a stable deep molecular response (DMR), has become an increasing option. However, many controversial aspects remain regarding treatment choices and timings, predictive factors, patient communication and optimal strategies aimed at achieving a successful TFR
Sex correlates with differences in long-term outcome in chronic myeloid leukaemia patients treated with imatinib
No full textManagement of elderly and unfit patients with chronic lymphocytic leukemia
Full text linkIntroduction: About 75% of patients with chronic lymphocytic leukemia (CLL) are more than 65 years at the time of diagnosis. Treatment of the elderly remains complicated due to multiple factors, such as comorbidities, decline in functional reserve and fitness. Since chronological age by itself cannot properly predict life expectancy and treatment tolerance, an accurate assessment of the fitness status is of crucial importance for an optimal treatment choice. Areas covered: This review will discuss the most relevant aspects concerning the issues experienced in the management of elderly/unfit patients with CLL. The most frequently observed age-related toxicities, fitness assessments, supportive care measures and treatment options for elderly patients and for patients who are deemed unfit will be discussed. Literature search methodology included examination of PubMed index. Expert commentary: During the last decade, different trials focusing on elderly/unfit patients have investigated more tolerable chemoimmunotherapy schedules and, more recently, the activity and safety of chemo-free regimens. Chlorambucil combined with an anti-CD20 monoclonal antibody has shown clinical activity with a relatively good profile of toxicity. The recent introduction of the B-cell receptor antagonists, ibrutinib and idelalisib, and other targeted drugs in development (e.g. venetoclax), is broadening the therapeutic armamentarium of elderly CLL patients
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