Management of elderly and unfit patients with chronic lymphocytic leukemia

Introduction: 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

Clinical characteristics and outcome of patients with autoimmune hemolytic anemia (AIHA) uniformly defined as primary by a diagnostic work-up

Primary autoimmune hemolytic anemia (P-AIHA) is a relatively uncommon and hetereogeneous disease characterized by the destruction of red blood cells due to anti-erythrocyte autoantibodies (AeAbs) in the absence of an associated disease [1–3]. Secondary AHIA is frequently associated with lymphoproliferative diseases (LD) in particular, chronic lymphocytic leukemia, aggressive or indolent lymphomas, autoimmune disorders, malignancies other than lymphoid, and infections [1,2,4]. On the hypothetical assumption that in a significant proportion of cases defined as P-AIHA the clinical heterogeneity could be due to an ignored associated disease, we retrospectively analyzed the clinical characteristics and outcome of patients with a diagnosis of P-AIHA based on a diagnostic work-up aimed at excluding or identifying an associated disease. ..

Improvement of bone marrow fibrosis with ruxolitinib: Will this finding change our perception of the drug?

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.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

There 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

Ponatinib induced improvement of cutaneous lesions associated to accelerated phase of Ph-positive chronic myeloid leukemia

Ponatinib a third generation tyrosine kinase inhibitor, has been approved for all phases of disease in CML. In advanced phase, has been confirmed with a good efficacy in all type of resistance, including T315I kinase domain mutation. We here report activity of the drug in advanced phase with extramedullary localization

Tyrosine kinase inhibitor discontinuation in the management of chronic myeloid leukemia: a critical review of the current practice

Introduction: 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

Changes in estimated glomerular filtration rate in chronic myeloid leukemia patients treated front line with available TKIs and correlation with cardiovascular events

We investigated the median estimated glomerular filtration rate (eGFR) changes in chronic myeloid leukemia (CML) patients treated front line with tyrosine kinase inhibitors (TKIs). A large cohort of 397 patients-320 treated front line with imatinib, 25 with dasatinib, and 53 with nilotinib-was retrospectively analyzed at a single institution. The eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration equation for all patients at baseline and then at 6 and 12 months, and at the last follow-up. Taking into account eGFR changes during the first year of treatment and excluding other possible cardiovascular risk factors, we considered also the percentage of cardiovascular events in patients with modifications of this single parameter. Imatinib induced a decrease in median eGFR (p = 0.01): 42 patients treated with imatinib had a cardiovascular event, related to modification of eGFR, in the absence of other cardiovascular risk factors. In patients treated with nilotinib, the median eGFR did not decline from baseline: only 1 patient experienced an ischemic event, but the eGFR remained unchanged. In patients treated with dasatinib, the mean eGFR did not change significantly: 3 patients experienced a cardiac ischemic event, but in all patients the eGFR remained unchanged over time, while advanced age and metabolic alterations contributed to the ischemic events. This long-term follow-up has documented that imatinib may induce changes in the eGFR, which may contribute to the onset of ischemic events. Further analyses on larger series of CML patients are required to conclusively define the potential renal toxicity of second generation TKIs and the consequent risk of developing ischemic events